Integrated Transcriptomic and Metabolomic Analysis of Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV) infected Lymantria dispar in Tree-top Disease

Integrated Transcriptomic and Metabolomic Analysis of Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV) infected Lymantria dispar in Tree-top Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Integrated Transcriptomic and Metabolomic Analysis of Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV) infected Lymantria dispar in Tree-top Disease Fengjiao Li, Yajie Wang, Xiao Yu, Dun Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-414994/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The pioneer record described the phenomenon of nucleopolyhedroviruses (NPVs) manipulating host behavior was named as Tree Top Disease or “Wipfelkrankheit” by Hofmann in 1891. Following publics advised multipartite effect during infection progressing that NPVs adjusting manipulated mode to actualize crossing barriers, immune escape and hormone regulation. In this study, the molecular mechanism of Lymantria dispar Multiple embedded Nucleopolyhedrovirus(LdMNPV)-infected was investigated by a comparison of transcriptomic and metabolomic analysis at four selected time points of LdMNPV-infected and healthy Lymantria dispar (Ld) larvae. Among data collecting, the notably up-regulated and down-regulated genes and metabolomics were used for further analysis. Integrative analysis revealed the content changes of caffeine, glutamate and gamma-Aminobutyric acid involved in LdMNPV inducing behavior change, and the alteration of myo-inositol, phosphatidyl-1D-myo-inositol and relevant genes involved in larval extended instar duration and apoptosis avoiding. Entomology Virology General Microbiology Tree Top Disease Lymantria dispar larvae pathway changes Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction In various parasites, host manipulating in protein transcription and expression, cellular metabolism, signal transduction and even behavior is substantive phenomenon, which is benefited to increase fecundity and transmission rates 1 – 3 . The baculoviruses provide an example of parasite-induced host manipulation, by which infection resulting in a series of obvious behavior change in the hosts. In retrospect, the intriguing phenomenon was first recorded in 1891 and was named “Tree Top Disease” or “Wipfelkrankheit” by Hofmann 4 . Till the late 1940s, it was confirmed the diseases causing by virus 5 . Baculoviruses are classified as a family of large rod-shaped circular double-stand DNA viruses, which specifically infect arthropods and have a unique replication 6 . Relying on the adaption for insect growth pattern and life cycle, the baculoviuses acquired a biphasic replication cycles, which including two individual virion phenotypes, the occlusion derived viruse (ODV) and the budded viruse (BV) 7 , 8 . The two viral forms, being genetically identical but morphologically different, preformed a synergistic action, giving expression to functions in both cell-to-cell (BV) and insect-to-insect (ODV) transmission, and also benefited for increasing efficiency of infection and virus titer 5 . On the other hand, the unique replication model causing the interaction mechanism between virus and host was time-ordered, dynamic and complicated, which hardly to be revealed. Baculoviruses lead typically abnormal behaviors on scheduling, which including increasing food intake, ELA, extended instar duration and climbing to elevated location before death 5 . As nonliving entity, virus needs to manipulate host cell program upon successfully infecting to survival and repilication. The effects of parasitifer infection were shown as behavior change in macroscopic aspect, which leading by manipulation of signaling transduction and alteration of cellular metabolism in microscopic aspect. The Enhanced Locomotory Activity (ELA) is typical early sign of baculoviruses infection 8 . In 3rd-instar Lymantria dispar larvae, the ELA was documented as appearing at average of 3.75 days post infection (dpi) and the phenomenon dying out at average of 4.75 dpi 9 , 10 . With systemic infection further expanding, ELA was the typical description of usurping caterpillar behavior, which normally occurred at healthy larval last instar and was administered by codeterminantion of larval physiological indexs like body size, hormone, phototaxis and geotaxis 11 . It is reported that in Bombyx mori the hormone metabolism manipulation is important to virus leading ELA 12 . The virus-induced climbing behavior also was refereed to such physiological alterations as geotaxis, phototaxis, vision, olfaction and rhythm 1 . Strinkly, the virus-induced climbing behavior happens in terminal, when the virus vastly replicating at all tissues, but the sick larvae still keep strong climbing ability. Goulson et al was hypothesized that the climbing behavior might be driven by sick larvae to get behavioral fever to respond to infection 4 . Investigations have suggested that the protein tyrosine phosphatase ( ptp ) gene is required for inducing the climbing behaviors in Group I Alphabaculovirus, including bombyx mori Nucleopolyhedrovirus(BmNPV) and AcMNPV 9 , 13 . In 2011, Hoover et al. reported that the ecdysteroid uridine 5’-diphosphate (UDP)-glucosyltransferase ( egt ) gene of LdMNPV was necessary to trigger the host behavior changes 14 . Similarly, the egt gene of Spodoptera exigua Multiple embedded Nucleopolyhedrovirus(SeMNPV) has been confirmed to have the same effect in hyperactivity and virus-induced climbing behavior 5 , 15 . By analyzing the transcriptome of silkworm larvae brains, it was reported that BmNPV-induced hyperactive behaviors were related to circadian rhythms, synaptic transmission and the serotonin receptor signal pathway 16 . Baculovirus were described to be equipped with photolyase-like genes, which have circadian clock regulation function and the UV-induced DNA repair activity 17 . Previous study was revealed that in LdMNPV-infected hyperactived larvae the photosensitivity was remarkably increased and the rhythmicity relevant genes, especially per and tim , was violently impacted 18 . The phenomenona occurring in host may operate by more complicated interaction as gene expression change, hormone regulation and metabolism alteration, which created by competition of control between parasite and host 19 , 20 . However, the mechanism by which NPV leading behavior changes is unclear. In the current study, based on the biphasic life pattern of virus and experience of larvae behavior alteration, four different time points were selected for the integrated analysis of transcriptomic and metabolomic comparison to be carried out. In order to reveal interactions between LdMNPV and Lymantria dispar and the interaction changes in chosen time points. Results Transcriptome sequencing and data analysis Before the analysis of transcriptome and metabolome, we drew the survival curve in LD90 (Lethal Dose, 90%) LdMNPV-infected and the result shown in Supplemental Figure S1. The curve shown two turning points in 72 and 144 hours post infenction (hpi). It is reported that the primary infection usually proceeded between 24 and 48 hpi, and the system infection occurred at later than 72 hpi 21 , 22 . Refer to infected larvae behavior change, LdMNPV biphasic infection mode and inflection points of survival curve are considered together, the 72 and 144 hpi (3 and 6 dpi) were chosen for analysis. Totally, we choose four time points as the newborn 3th-instar larvae (NB3), 72 hours 3th-instar larvae post mock-infected (CK3), 72 hours 3th-instar larvae post infected (Ld3) and 144 hours 3th-instar larvae post infected (Ld6). The chosen time point NB3 as starting point to afford contral and reference. The chosen time point Ld3 (3 dpi) indicate the progress of systemic infection, extensively intruded other organizations and massive replication. And the chosen time point Ld6 (6 dpi) indicated the infection larvaes were faced with imminent death. Because of the mock-infected larvae molt at 4 days old, we choose the 3 days old mock-infected larvae as contral groups. Four groups (NB3, CK3, Ld3 and Ld6) from twelve samples of L. dispar larvae transcriptomic sequencing respectively generated 63,602,453, 61,981,656, 60,543,314 and 60,633,947 raw reads, and was produced with an average insert size of 298.98bp. In all libraries more than 93.37% of the sequences had a quality score greater than Q30 (Supplemental Table. S1), which indicates that all libraries obtained high-quality raw reads. After qualities were filtered and de novo assembled, the clean reads were totally assembled into 56,923 unigenes by Trinity software, which represents 73.78 Gb of the transcription data. The average length of the unigenes was 1083.78bp, and the N50 was 1877bp (Supplemental Table S2; Supplemental Fig. S2A). The functional identity of all unigenes was investigated. Homologous annotation for all unigenes was based on information within the GO, Pfam, Swissporot, KOG, eggNOG, Nr, and KEGG databases. Consequently, 26,562 unigenes were annotated at least in one database (Supplemental Table S3). The box-plot figure of all samples is exhibited in Supplemental Figure S2B, of which the FPKM (Fragments Per Kilobase of transcript per Million mapped reads) was used to describe the degree of discretization as evaluation criteria of the gene expression level. The Pearson correlation between the groups is an important parameter, which reflects the experimental reliability and indicates whether the sample selection is reasonable or not. The Pearson correlation and the correlation plot between two samples are exhibited in Supplemental Figure S2C. By using the DESeq2 softwave, parameters were set as FDK (false discovery rate) < 0.01 and FC (fold change) ≥ 2; the unigenes from each of the two groups were compared to acquire the different expression genes (DEGs). The results list in Supplemental Table S4. The Cluster analysis was shown in Fig. 1 A. It is indicated that the CK3, Ld3 and Ld6 were grouped together and separated with NB3, and the CK3 and Ld3 were similary than others groups also reveal the difference in infection proceeding. The MA-plot (Supplemental Fig. S3A-E) clearly reveals the overall distribution of gene expression levels and fold changes. And the results of MA-plot indicated that the unchanged genes distribution in Ld3 versus Ld6 was exhibited in fusiform, which was different with other groups. Based on the gene expression in the different samples, to identify the annotation of DEGs function, the number of annotated DEGs in different databases is listed as in Supplemental Table S5. In GO annotations, these unigenes were divided into 53 categories belonging to biological processes, cellular components and molecular functions. The DEGs were specified to GO categories to determine functional classifications. Related to biological process, most DEGs were involved in metabolic processes, cellular processes, single-organism processes, biological regulation, localization and response to stimulus. In the cellular component, the DEGs were involved in cells, cell parts, membranes, membrane parts and extracellular regions. In molecular functions, most GO terms concentrated upon binding and catalytic activity. The results of GO database annotated DEGs between groups were shown in Supplement Figure S4. In KEGG annotations, a total of 10,157 unigenes were mapped onto 303 different KEGG pathways found in human diseases, genetic information processing, metabolism, organismal systems, environmental information processing and cellular processes in six categories. The stacking bar chart of DEGs was shown in Fig. 1 B. In general, in NB3 versus CK3 and Ld3 versus Ld6, the number of up regulation DEGs is more than down, and the amount of DEGs is smallest in Ld3 versus Ld6. It is also indicated that the immune system was not obviously activate in infection larvae, but Signal transduction, Xenobiotics biodegradation and metabolism, Carbohydrate metabolism and Lipid metabolism were significant enriched. Additionally, Replication and repair and Folding, sorting and degradation were drastic change with infection process. The Supplemental Table S6 list out the top 3 of drastic changed, up-regulated and down-regulated pathways, which were annotated between groups. And the bubble diagrams of pathway enrichment are shown in Fig. 1 C- 1 G. According to that, we summarized that between two un-infection groups, NB3 versus CK3, the DEGs mainly enriched in small bioactive molecule metabolism like vitamin and cofactor, the extracellular matrix (ECM)-receptor interaction and the defense to external environment. The two compares, NB3 with Ld3 and NB3 with Ld6, mostly give expression to carbon and amino acid metabolism. Between Ld3 and Ld6, the DEGs enrichment pathways tend to focus on cell supporting in material. Especially the carbon metabolism pathway and biosynthesis of amino acids pathway both were drastic down regulated. But the glycosphingolipid biosynthesis pathway was increased. In CK3 versus Ld3, the enriched pathways involved ribosome cytochrome P450 and energy metabolism, which implicates alteration provide the condition of viral genome replication and satisfy the energy supply. Furthermore, the DEGs were compared with the COG database(Cluster of Orthologous Groups of proteins)and resulted in 26 different functional categories (Supplemental Fig. S5). The DEGs also were annotated to the eggNOG database in different functional categories (Supplemental Fig. S6). Each of them provides panoramic account DEGs between groups from different angles. Comparing with the DEGs annotations, the GSEA emphasizes the gene, which plays an important biological effect but only have a subtle change of expression, by enrichment the gene sets. The GESA result, which visualization by Cytoscape, was shown in Figure (Fig. 2 A- 2 E). The topological structure describes the correlation characteristic of gene set, which combines the Jaccard similarity coefficient standard by distance and the overlap coefficient standard by green line. To separate different patterns, we pained the nodes background as violet represents metabolism, aqua represents genetic information processing, and pink represents environmental information processing. Generally, it is shown that in combination as NB3 versus Ld3 and NB3 versus Ld6 the enriched gene sets are numerous in quantity, means larger variations in these two groups. Between NB3 and CK3, the enriched gene sets involved material metabolism and surroundings signal receptor, like phototransduction-fly and neuroactive ligand-receptor interaction, reflecting the larval physiological change of growing process. In the combination as NB3 versus Ld3 and NB3 versus Ld6 the associating gene sets, most of which present an up-regulated trend, mainly included cellular nutrition utilization, energy metabolism and material metabolism, which is shown as complicated network painted in violet background. In this two comparison, the up-regulated gene sets were peroxisome, phototransduction-fly and insect hormone biosynthesis, the down-regulated gene sets were lysosome, apoptosis, proteasome, ubiquitin-mediated proteolysis, endocytosis regulation of autophagy, dorso ventral axis formation, protein export and ABC transporters. Compared with the group NB3 versus Ld3, the trend of group NB3 versus Ld6 enriched gene sets integrally appears down-regulation and the scanty up-regulated gene sets focused on energy and material metabolism. As the infection progresses further, it is revealed that in Ld3 versus Ld6 the alteration mainly consists of material metabolism and protein export, especially in fatty acid metabolism. Other gene sets were peroxisome, protein export and neuroactive ligand-receptor interaction. And the down-regulation emphasized the apoptosis. Between CK3 and Ld3, only the Citrate cycle (TCA cycle) and tyrosine metabolism showed the up-regulation. The down-regulated gene sets covered maintenance and development signal and genetic information processing. The decreasing extensively pathways of host genetic information processing accords with the viral manipulation in early replication. The transcriptomic analysis shown that after being infected, the metabolism, signal transductions and detoxication relevant metabolism of L. dispar larvae were visibly affected, but immune function relevant pathways, like the JAK/STAT signaling pathway, NF/kB signaling pathway and Toll-like Receptors pathway, were not significantly affected. Further more, with infection progressing, the apoptosis was continuous down-regulation. Metabolite extraction and analysis Other than protein-interaction, metabolism is constituted by chemical reactions, which is described metabolites as nodes and functional proteins as edges. Metabolomic analysis of twenty-four samples from four groups (NB3, CK3, Ld3 and Ld6) of L. dispar larvae was performed via UHPLC-QTOF-MS. As a result, 1,930 and 1,831 metabolins were respectively obtained using POS and NEG mode detection. Based on the PCA Analysis (Supplement Fig. S7) and Cluster Analysis (Fig. 3 A-B), the qualified metabolite data was subjected to differential analysis. After the metabolites were detected by the qualitative analysis, the quantities were compared between groups to show the extent the metabolites changed. The standard P-value 2 of OPLS-DA were used to screen the different metabolites. The amount of different metabolites between groups was shown in Table 1 . To shown the variability we clustered the different metabolins, the result was shown in Supplemental Figure S8. And the Wayne diagram exhibits in all groups the relationship of the change in metabolites (Fig. 3 C-D). Taken together, the results reflected that in all comparatives the metabolite changes in NB3 versus CK3 and Ld3 versus Ld6 were easement, but in CK3 versus Ld3 was fierce. To identify the pathways of metabolites involved, a total of 1,359 metabolites in the POS mode and 1,341 metabolites in the NEG mode were mapped to KEGG metabolic pathways; in POS and NEG mode, the stacking bar charts of different metabolites in KEGG enrichment were shown in Fig. 3 E-F; the details are listed in Table 1 ; and the bubble diagram of different metabolites in KEGG enrichment were shown in Fig. 3 G-P. The stacking bar charts were shown that LdMNPV leading a largescale alteration in metabolism and organismal systems of infected larvae. The results revealed that the different metabolites annotated into KEGG database were concentrated in some key pathways. Generally, in POS mode, metabolic pathway, ABC-transporters and biosynthesis of amino acid were indicated to undergo a violent change in all comparisons. An exception to the above is that protein digestion and absorption emerged in NB3 versus CK3, NB3 versus Ld3,Ld3 versus Ld6, and CK3 versus Ld3. Meanwhile in NB3 versus Ld6, it is shown as glycerophospholipid metabolism. In NEG mode, metabolic pathway, biosynthesis of amino acid, 2-Oxocarboxylic acid metabolism and ABC-transporters were indicated to a violent change in all comparisons. An exception to above, the central carbon metabolism in cancer emerged in NB3 versus Ld3, NB3 versus Ld6 and CK3 versus Ld3; the protein digestion and absorption emerged in NB3 versus CK3, Ld3 versus Ld6 and CK3 versus Ld3; moreover in CK3 versus Ld3, it is shown as aminoacyl-tRNA biosynthesis and biosynthesis of unsaturated fatty acids. The metabolomics analysis has shown that the LdMNPV induced a largescale alteration in cellular metabolism of infected larvae. In normal physiology status, from NB3 to CK3, the different metabolites, which were enriched into metabolism pathways evenly distribute in amino acid, lipids, and other small molecular metabolistes. After be infected, from CK3 to Ld3, the pathways including amino sugar and nucleotide sugar metabolism, biosynthesis of unsaturated fatty acid biotin metabolism, D-glutamine and D-glutamate metabolism, nitrogen metabolism and galactose metabolism were enriched dramatic change. From Ld3 to Ld6, arginine biosynthesis, galactose metabolism, purine metabolism, amino sugar and nucleotide sugar metabolism, fatty acid biosynthesis and galactose metabolism pathways were enriched further change. Though different viruses appear to activate different metabolic altering pattern, the reprogramming of host cell is determinant to viral growth. In this context, it was pertinent to conclude that the alteration in fatty acid synthesis, carbon source utilization and biosynthesis of amino acid was changed to guarantee optimal microenvironment for LdMNPV’s replication and spread. Other wise, after infection the GABAergic synapse, cholinergic synapse, doparninergic synapse, glutarnatergic synapse, neuroactive ligand-receptor interaction and phosphatidylinositol signaling system also constant with infection processing, indicating the viral infection may affect on host’s nervous and signal transduction. Integrative analysis of metabolome and transcriptome To explore further dynamic variation of the infection-caused behavior change in L. dispar , an integrated and detailed analysis was performed on the transcript and metabolic levels. Before screening data, the Pearson correlation coefficient (PCC) and corresponding P-value were used to filtrate the data simultaneously, with values set to PCC > 0.80 and PCCP < 0.05. Totally, the integrative analysis of metabolome and transcriptome screens 52 pathways in the POS mode and 56 pathways in the NEG mode. The amount of different expression genes and metabolites in KEGG pathway was list on Table. 2. The Wayne diagram exhibits in all groups the relationship of the change in covering KEGG pathways (Fig. 4 A-B). The stacking bar charts of different expression genes and metabolites in KEGG classification in POS and NEG mode were shown in Fig. 4 C and corresponding quantity of different expression genes and metabolites in each KEGG classification were shown in Fig. 4 D-E. The results showed that in POS mode the specific differences in NB3 versus CK3 and Ld3 versus Ld6 are covering more KEGG pathways than other compares, but in NEG mode it have more similarity. In general, Global and overview maps, Carbohydrate metabolism and Amino acid metabolism present significant difference in both of POS and NEG mode, but the amount of difference expression genes and metabolites in Ld3 versus Ld6 were smaller than others, especially the CK3 versus Ld3. Strikingly, the difference of energy metabolism were appeared at POS mode in NB3 versus CK3 and Ld3 versus Ld6, and at NEG mode in NB3 versus Ld3, NB3 versus Ld6 and CK3 versus Ld3. The interaction and enrichment frequency of covering KEGG pathways were visualized in Fig. 4 F to dig out more details. The figure showed that Carbohydrate metabolism, Amino acid metabolism and Lipid metabolism were enriched to most pathways, as Carbohydrate metabolism have 15 pathways, Amino acid metabolism have 14 pathways, and Lipid metabolism have 11 pathways. The KEGG classifications of Global and overview maps and Nucleotide metabolism were violently fluctuation. What’s more, the Alanine, aspartate and glutamate metabolism pathway, Lysine degradation pathway and Tyrosine metabolism pathway in Amino acid metabolism, Glycerophospholipid metabolism pathway in Lipid metabolism, ABC transporters pathway in Translation and neuroactive ligand-receptor interaction pathway in Membrane transport were also drastic fluctuation. Further analysis showed that the specific enriched KEGG pathways were arachidonic acid metabolism, propanoate metabolism, mTOR signaling pathway, parkinson disease and alcoholism in NB3 versus CK3; oxidative phosphorylation in NB3 versus Ld3; D-Glutamine and D-glutamate metabolism, nicotinate and nicotinamide metabolism, one carbon pool by folate and FoxO signaling pathway in Ld3 versus Ld6; and glycerolipid metabolismin CK3 versus Ld3. Except the 54 pathways of each metabolism classifications, other enrichment only covered 10 pathways, including aminoacyl-tRNA biosynthesis pathway, ABC transporters pathway, FoxO signaling pathway, phosphatidylinositol signaling system, neuroactive ligand-receptor interaction pathway, mTOR signaling pathway, protein digestion and absorption pathway, bile secretion pathway, parkinson disease pathway and alcoholism pathway. Among them, the ABC transporters pathway only keeps invariant in NB3 versus CK3 in NEG mode, which showed severe change. The aminoacyl-tRNA biosynthesis pathway was enriched in NB3 versus Ld3, NB3 versus Ld6 and CK3 versus Ld3 in both POS and NEG mode. The protein digestion and absorption pathway was enriched in NB3 versus Ld3 and NB3 versus Ld6 in both POS and NEG mode. The bile secretion pathway shows slight variation in NB3 versus CK3 and NB3 versus Ld6 in POS mode, and in NB3 versus Ld6 in NEG mode. The mTOR signaling pathway, parkinson disease and alcoholism were only changed in NB3 versus CK3,and the FoxO signaling pathway was only changed in Ld3 versus Ld6. It is remarkable that the changes of neuroactive ligand-receptor interaction pathway and phosphatidylinositol signaling system pathway, which showed incompatibility in POS and NEG mode. The change of neuroactive ligand-receptor interaction pathway appears at NB3 versus CK3, NB3 versus Ld3, Ld3 versus Ld6 and CK3 versus Ld3 in POS mode, and at NB3 versus Ld6 and CK3 versus Ld3 in NEG mode. And the change of phosphatidylinositol signaling system pathway occurs at CK3 versus Ld3 in POS mode, and at NB3 versus Ld3, Ld3 versus Ld6 and CK3 versus Ld3 in NEG mode. By comparing the different metabolites, it is reveal that in neuroactive ligand-receptor interaction pathway the incompatibility causing by detection of dopamine, acetylcholine, adenosine and trace amine were different in POS and NEG mode, and in phosphatidylinositol signaling system pathway was phosphatidyl-1D-myo-inositol (PI). Based on the interaction of KEGG pathways and dynamic change between each groups, it is filter out that the change of neurotransmitter, cyclohexanehexol and secondary metabolism may associate with host-parasites interaction. The neurotransmitter like dopamine and acetylcholine, increase in NB3 versus CK3 but remain stable in other compares. The caffeine metabolism pathway was enriched in NB3 versus Ld3 and CK3 versus Ld3. In CK3 versus Ld3, the caffeine was increase, and xanthine dehydrogenase/oxidase (XDH) gene was decrease, which relevant to purine metabolism by oxidizing xanthine. In C.elegans and Drosophila melanogaster cyclohexanehexol was reported to extend lifespan 23 , 24 . The inositol phosphate metabolism pathway and phosphatidylinositol signaling system pathway were both enriched in CK3 versus Ld3 and Ld3 versus Ld6, which two pathways link by cyclohexanehexol. In CK3 versus Ld3, the myo-inositol (MI) was increase and PI was decrease. The inositol polyphosphate 5-phosphatase (INPP5A) and phosphatidylinositol-4-phosphate 3-kinase (PI3K) gene were upregulated and inositol 1,4,5-triphosphate receptor (IP3R) gene was downregulated. And in Ld3 versus Ld6, the PI was increase and MI was decrease. Meanwhile, the phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (PTEN/MMAC1), multiple inositol-polyphosphate phosphatase/2,3-bisphosphoglycerate 3-phosphatase (MINPP1) and ip3r gene were up-regulated, and the pi3k gene was down-regulated. Other metabolisms like pyruvate, N-acetylglucosamine (GluNAc) and NAD + also relevant to life prolonging. Among them, only GluNAc was increase, which was enriched in Ld3 versus Ld6. In Bombyx mori , after BmNPV infection the trehalose, malate, fumarate, citrate, succinate, α-ketoglutarate, phenylalanine and tyrosine showed accumulate in the resistant strain YeA, but in susceptible strain YeB the gluconate, glutamate and aspartate were upregulation 25 . The results showed the phenylalanine and tyrosine were kept increasing in CK3 versus Ld3 and Ld3 versus Ld6. In Arginine biosynthesis pathway the different metabolites were glutamine, glutamate and citruline, which show changing consistency. In NB3 versus CK3 this three all decreases, with glutamine synthetase (GS) gene, glutamate dehydrogenase (GDH) gene, acylamide amidohydrolase (ASL) gene and amido acid deacylase gene were downregulated, and NADPH-diaphorase gene was upregulated. In CK3 versus Ld3 and Ld3 versus Ld6, the glutamine, glutamate and citruline keep accumulate, but genes expression were altered. In CK3 versus Ld3, gs gene, gdh gene, asl gene and arginosuccinate synthetase (ASS1) gene were upregulated, amido acid deacylase gene was downregulated. In Ld3 versus Ld6, gs gene, and NAD(P) + oxidoreductase gene were upregulated, NADPH-diaphorase gene was downregulated. Moreover, in Ld3 versus Ld6 glutamate as the principal excitatory amino acid neurotransmitters, accumulate indicate targeted utilization by glutamine synthetase (GLUL) gene upregulated, which product was glutamine showed increase. And the glutamate decarboxylase gene was downregulated keeping the content of it product, gamma-Aminobutyric acid (GABA) working as a chief inhibitory neurotransmitter in reducing neuronal excitability, remains stable. The carbohydrate metabolism also revealed noteworthy change after infection. In CK3 versus Ld3, the alpha-D-glucoside glucohydrolase gene and alpha-D-galactoside galactohydrolase gene were upregulated, causing accumulate of galactinol, raffinose, sucrose, stachyose, mannose and MI. Than in Ld3 versus Ld6, the expression level of alpha-D-glucoside glucohydrolase gene and alpha-D-galactoside galactohydrolase gene remained stable, but the galactinol, raffinose, sucrose, mannose and MI present lack. Discussion Infection with a wide variety of parasites, including baculovirus, can result in behavior changes in the host. For survival and replication, the parasites have to conquer host defenses barriers of immunity, even manipulate the host’s physiology 1 – 3 . Some reports have provided insight into how baculovirus producing influences on host, depending on some core genes or even just one gene 9 , 13 – 16 . Within the last decade, the primary host behavior manipulation gene of NPV had been brought to light 5 , 9 , 13 – 18 , 26 – 29 . The details on host reacting and its mechanism to virus-induced activity rarely had been addressed. In this study, through the integrative analysis of metabolome and transcriptome between the key time points, which were chosen by critical moment of replication characteration and infected host larval behavior changes, and we sum up the alteration of MI, PI and relevant genes involved in larval extended instar duration, and the changes of caffeine, glutamate and GABA involved in LdMNPV inducing behavior change. Parasites are capable of inducing host behavior alterations in many aspects to increase transmission rates 1 – 3 , 5 . The NPV infection triggered abnormal physiological status, like increasing food intake, ELA, extended instar duration and climbing to elevated location before death foraging 5 , which leading by alteration of host cellular metabolism and manipulation of signaling transduction. The infected L. dispar larvae had prolonged their 3th instar duration, which was 4 to 5 days in healthy larvae, to 7 to 8 days 10 . The survival curve in LD90 of LdMNPV-infection (Supplemental Figure S1) was shown that the 3 and 6 dpi were two inflection points. Baculoviuses specially have a biphasic replication cycle, which including two individual virion phenotypes, the ODV and the BV 5 , 7 . The ODV and BV were genetically identical but morphologically different, which also were related-time produnction. Combined with the biphasic infections and the early infection mainly happening in midgut which only regional impact, the time point Ld3 and Ld6 were chosen to indicate the proceeding of systemic infection at early and imminent stages of massive replication. In the four groups (NB3, CK3, Ld3 and Ld6) of L. dispar larvae, twelve transcriptomic samples were sequenced. On the whole, the CK3 and Ld3 were more similary than others groups (Fig. 1 A). Based on DEGs annotation, it is showed that the pattern of NB3 versus CK3 and Ld3 versus Ld6 were approximate, and the alteration in cellular mainly concentrates on benefiting virus DNA replication, the energy supply and detoxication relevant metabolism were visibly affected, and immune function relevant pathways, like the JAK/STAT signaling pathway, NF/kB signaling pathway and Toll-like receptors pathway, were not significantly affected (Fig. 1 B). After being infenction, the DEGs analysis showed regulatory strategy change in different infection stages, involving affect material supply of virion production and anti-apoptosis to prolong infected cell survival. Furthermore, by KEGG annotations, the DEGs enrichment showed that between CK3 and Ld3, the violently upregulated pathways were metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450 and galactose metabolism; and the drastically downregulated pathways were ribosome, carbon metabolism and phagosome, which reveals alteration provide the condition of viral replication, alteration of energy supply and avoid cell damage, toxin and reactive oxygen species (ROS) stress causing by virus repilication. Between Ld3 and Ld6, the violently upregulated pathways were carbon metabolism, phenylalanine metabolism and biosynthesis of amino acids; and the drastically downregulated pathways were lysosome, mTOR signaling pathway and longevity regulating pathway-multiple species. The upregulated of carbon metabolism, phenylalanine metabolism and biosynthesis of amino acids confirmed infection causing globally alteration of material utilization. The downregulated of lysosome, mTOR signaling pathway and longevity regulating pathway were benefit in keeping host cell survival. The genes, which were enrichment in lysosome pathway involving in metabolism disorder, and the upregulated gene could promote glycerolipid collection 30 . The drastic changes of longevity regulating pathway may relate to prolonging instar duration of infected larvae. It is also reported that dietary restriction and genetic down-regulation of nutrient-sensing pathways, like Insulin-like signaling pathway and mTOR signaling pathway can substantially increase life span 31 . Generally, the GESA result (Fig. 2 A-E) is shown that NB3 versus Ld3 and NB3 versus Ld6 the gene sets which were enriched in have more volume, reveals the larger variations in these two comparisons. From NB3 to CK3 (Fig. 2 A), the enrichment was involved in material metabolism and surroundings signal receptor, which reflecting the larval physiological change of growing process. Between CK3 and Ld3 (Fig. 2 E), only the Citrate cycle (TCA cycle) and tyrosine metabolism showed the upregulation, and lots of gene sets downregulated mainly covered maintenance and development signal and genetic information processing, which was accords with the viral manipulation in early replication. The transcriptomic analysis shown that pathways of metabolism, signal transductions and detoxication relevant metabolism were visibly affected in infection L. dispar larvae. Further more, with the infection proceeding, it is revealed that in Ld3 versus Ld6 (Fig. 2 D) the alteration mainly consists of material metabolism and protein export, especially in fatty acid metabolism, and the apoptosis was continuous downregulation. Twenty-four metabolomics samples obtained 1,930 metabolins in POS mode and 1,831 metabolins in NEG mode. In contrast between groups, a large variety of metabolites show significant reduction in the virion production stages (Fig. 3 A-B). Results of the amount of different metabolites between groups, the variability of different metabolins and the Wayne diagrams (Fig. 3 C-F) reflected that the metabolite changes in NB3 versus CK3 and Ld3 versus Ld6 were easement, but in CK3 versus Ld3 was fierce. The metabolin enrichment showed the metabolic pathway, ABC-transporters, 2-Oxocarboxylic acid metabolism, biosynthesis of amino acid and protein digestion and absorption merged to produce a violent change in all comparisons. Meanwhile, the alteration of central carbon metabolism in cancer, which was accredited in lots of human source virus infections, only emerged in NB3 versus Ld3, NB3 versus Ld6 and CK3 versus Ld3. In rapidly replication viruses, the hyper-activation of sustained metabolic pathways was sufficed to increasing viral titers 32 , 33 . The results of different metabolites KEGG enrichment revealed that the different metabolites were concentrated in some key pathways. From NB3 to CK3, as normal physiology status, the different metabolites have been enriched evenly distribute in amino acid, lipids, and other small molecular metabolistes. After be infected, from CK3 to Ld3, the enriched pathways covering amino sugar and nucleotide sugar metabolism, biosynthesis of unsaturated fatty acid biotin metabolism, D-glutamine and D-glutamate metabolism, nitrogen metabolism and galactose metabolism were enriched dramatic change. The nutrients uptake and utilization alteration tend to provide enough ATP to meet the energy costs of virus DNA replication. The increasing of lipid material was induced by the needed of additional membrane material for the viral particle envelopment. Though different viruses appear to activate different metabolic altering pattern, the reprogramming of host cell is determinant to viral growth. Since Munger et al reporting the first eukaryotic virus tampering cellular metabolomics, different studies shown variously manipulate multiple major metabolic pathways to reprogram host cellular nutrients uptake and utilization to meet the increasing material and energy costs to guarantee the optimal microenvironment 34 – 38 . The research also shown that the viruses inducing aerobic glycolysis as known as the “Warburg effect” 32 , 33 . The alterations of nutrients uptake and utilization could provide ATP in a rapid fashion to meet the high energy costs and avoid cell ROS stress of virus replication, and the increasing of lipids by altering the fatty acid synthesis, is needed to afford the additional membrane material for the viral particle envelopment. In comprehensive consideration of existing research and the data of transcription and metabolism, more detail about LdMNPV and host interaction was uncovered. The integrative analysis of metabolome and transcriptome totally enriched 52 correlational pathways in the POS mode and 56 correlational pathways in the NEG mode. The results showed that the specific differences in NB3 versus CK3 (physiological status) and Ld3 versus Ld6 were covering more KEGG pathways with less enrichment amount of different express genes and metabolites, between which have more similarity than others compares (Fig. 4 A-C). The Global and overview maps, Carbohydrate metabolism and Amino acid metabolism present significant difference in both of POS and NEG mode (Fig. 4 C), but the amount of difference expression genes and metabolites in Ld3 versus Ld6 were smaller than others, especially the CK3 versus Ld3 (Fig. 4 D-E). Comparing with the normal physiological status, the alteration of infected status refers to signal transduction, nucleotide metabolism, fatty acid metabolism, amino acid metabolism and cofactors metabolism. The figure.4F and table.2 were showed that Carbohydrate metabolism, Amino acid metabolism and Lipid metabolism were enriched to most pathways, Carbohydrate metabolism have 15 pathways, Amino acid metabolism have 14 pathways, and Lipid metabolism have 11 pathways. In metabolism relevant pathway the dynamic change of the Alanine, aspartate and glutamate metabolism pathway, Lysine degradation pathway and Tyrosine metabolism pathway in Amino acid metabolism, Glycerophospholipid metabolism pathway in Lipid metabolism, ABC transporters pathway in Translation and neuroactive ligand-receptor interaction pathway in Membrane transport were striking. It is showed that the specific enriched KEGG pathways were arachidonic acid metabolism, propanoate metabolism, mTOR signaling pathway, parkinson disease and alcoholism in NB3 versus CK3; oxidative phosphorylation in NB3 versus Ld3; D-Glutamine and D-glutamate metabolism, nicotinate and nicotinamide metabolism, one carbon pool by folate and FoxO signaling pathway in Ld3 versus Ld6; and glycerolipid metabolismin CK3 versus Ld3. For another, the enrichments excepting metabolism relevant only covered 10 pathways, including aminoacyl-tRNA biosynthesis pathway, neuroactive ligand-receptor interaction pathway, ABC transporters pathway, phosphatidylinositol signaling system, FoxO signaling pathway, mTOR signaling pathway, protein digestion and absorption pathway, bile secretion pathway, parkinson disease pathway and alcoholism pathway. Except the aminoacyl-tRNA biosynthesis pathway, neuroactive ligand-receptor interaction pathway, ABC transporters pathway and phosphatidylinositol signaling system, the others just change a few in limited compares. The aminoacyl-tRNA biosynthesis pathway was violent alteration in CK3 versus Ld3, reflecting that the reprogram of host cell transcription preferences which leading by LdMNPV. There have not enrichment any difference in Ld3 versus Ld6, which means alteration of aminoacyl-tRNAs were keeping stable with infection processing. Moreover, it is reported that after infected by BmNPV in Bombyx mori larvae the trehalose, malate, fumarate, citrate, succinate, α-ketoglutarate, phenylalanine and tyrosine were accumulated in the resistant strain YeA, but in susceptible strain YeB the gluconate, glutamate and aspartate showed upregulation 25 . The integrative analysis showed in L. dispar larvae the phenylalanine, tyrosine, gluconate and glutamate were continued accumulation in CK3 versus Ld3 and Ld3 versus Ld6, which revealed different patterns of host-virus interaction. The gluconate and glutamate were gived further attention, in Ld3 versus Ld6, the accumulation glutamate indicate targeted utilization by glul gene upregulated leading glutamine showed increase and the glutamate decarboxylase gene was downregulated causing GABA, a chief inhibitory neurotransmitter, remains stable. In the insect central nervous system (CNS), GABA and glutamate working as antagonists and agonists in neuronal excitability control 39 – 42 . It is showed that GABA and glutamate are involved in the mediation of aggressive behavior in invertebrates 43 . In honeybee, the connection between scouting behaviors and catecholamine, glutamate and GABA reflect effects of neurotransmitter to behaviors, and glutamate treatments increased the probability of foragers scouting behaviors 42 . Moreover, in CK3 versus Ld3 the caffeine was increase. It is reasonable to consider that content patterns of caffeine, glutamate and GABA involved in LdMNPV inducing behavior change. Metabolisms like spermidine, pyruvate, GluNAc and NAD + were relevanted to life prolonging 44 – 47 . Among them, only GluNAc showed increasing, which was enriched in Ld3 versus Ld6. In C.elegans and Drosophila melanogaster cyclohexanehexol was reported to extend lifespan 23 , 24 , 49 . The inositol phosphate metabolism pathway and phosphatidylinositol signaling system pathway, which linking by cyclohexanehexol, were both enriched after LdMNPV infection. In CK3 versus Ld3, the MI was increase and PI was decrease, and relevent genes, the inn5a and pi3k were upregulated, and pi3r gene was downregulated. And in Ld3 versus Ld6, the PI was increase and MI was decrease, and the pten/mmac1 , minpp1 and ip3r gene were upregulated, the pi3k gene was downregulated. As important second messenger, the phosphatidylinositol-3,4,5-triphosphate (PIP3) mediated lots of intracellular signaling molecule which was activating types of growth factors, cellular stimulus or toxic insults and regulates fundamental functions affected transcription, cell cycle progression, proliferation and survival 50 , 51 , that keeping stable in all groups. The accumulation of PIP3 in cell will trigger stress resistant and apoptosis. Moreover, intracellular phospholipid signal involved in managing endocytic and exocytic processes, regulating iron channaels, pumps and transporters, coordinating vesicular trafficking and modulating lipid distribution and metabolism 52 . Numbers of pathogens, especially virus, has been recognized reprogram cellular processes by hijack host cell phospholipid signal 53 . Refer to alteraction of the inositol phosphate metabolism pathway and phosphatidylinositol signaling system pathway in infected larvae, it is hypothesis that MI, PI and relevant genes involving in larval extended instar duration and apoptosis avoiding. Considering all the results, LdMNPV biphasic infection mode causing host manipulation changes continuously in different time points of infection. Comparing with the normal physiological status, alterations of nutrients uptake and utilization could provide ATP in a rapid fashion to meet the high energy costs and avoid cell stress resistant and apoptosis of virus replication, and the increasing of lipids by altering the fatty acid synthesis, is needed to afford the additional membrane material for the viral particle envelopment, and immune function relevant pathways were not significantly affected. Moreover, maintaining infected cell stability is important to virion production and assembly at terminal of infection and the extended instar duration of host was benefitted to virus production. In summary, we explored the complicated interactions between LdMNPV and 3th-instar L. dispar larvae at the metabolome and transcriptome levels, conducted the preliminary analysis, uncovered that the content patterns of caffeine, glutamate and GABA involved in LdMNPV inducing behavior change, and the MI, PI and relevant genes involving in larval extended instar duration and apoptosis avoiding. It is anticipated that further research in relevent pathways will reveal in the complex reactions in conflict between L. dispar and LdMNPV. Materials And Methods Insect and virus L. dispar eggs were provided of Professor Liang-Jian Qu from the Chinese Academy of Forestry, Beijing, China. Hatched larvae were raised on artificial diet in a sterile phytotron with conditions as follows: temperature 26 ± 1°C, Relative Humidity 60 ± 5% and the photoperiod of 14: 10 (Light: Dark). LdMNPV was stored in the laboratory. The ODV s was obtained from inoculated larvae, and prepared by the following steps. Inoculated larvae were washed with 0.25% sodium dodecyl sulfate filtered through filter paper and cheesecloth. Filtrate is washed twice with double-distilled water and centrifuged at 3000rpm for 30mins. The precipitate was re-suspended with double-distilled water and quantified using a bacterial counting chamber, and diluted to the final concentration of 10 9 occlusion bodies (ODVs)/mL. The virus suspensions were stored at 4°C. Sample preparation Newly molted third-instar larvae were used as the experimental subjects and were randomly divided into two groups: infection group and control group. Larvae of the infection group were fed with 10 6 OBs per larva of LdMNPV. For the control group, the isopyknic double-distilled water was provided using the same method. After having been fed, larvae were reared in a 24-well insect rearing box in individual wells with ample artificial diet in each well. Samples for transcriptome and metabolome analysis were obtained at the newly-molted third-instar larvae (NB3) stage,at 72 hours after treatment for the control group (CK3), at 72 hours after treatment for the LdMNPV infected group (Ld3), and 144 hours after treatment for the LdMNPV infected group (Ld6). The control group did not have any samples at 144 hours after treatment because mock-treated larvae molted into the next instar before 144 hours. Meanwhile༌surplus larvae from each group were kept to confirm the treatment was working. Death for infection was committed by liquefaction, and another group was observed till pupation. Sampled larvae were snap frozen in liquid nitrogen more than 24 hours and stored at − 80°C until further steps. Transcriptome sequencing and data analysis Total RNA was extracted from the intact samples by using TRIzol Reagent (Invitrogen) following the protocol of the manufacturer. Quality of RNA-samples was checked on 1% agarose-gel and the concentration were measured using NanoDrop 2000 (Thermo). Sequencing libraries were generated using NEBNext®Ultra™ RNA Library Prep Kit for Illumina® (NEB, USA) and purified by AMPure XP system (Beckman Coulter, Beverly, USA). All cDNA libraries sequencing were performed at Biomarker Company (Beijing, China; http://www.biomarker.com.cn ). The raw data were processed through in-house perl scripts and the clean data Q20, Q30, and GC content were calculated. The clean data using for RNA de novo assembly by Trinity 54 which setting like min_kmer_cov as 2 and all others by default. Assembled transcript functions were annotated based on the NCBI non-redundant protein sequences (Nr), Protein family (Pfam), Swiss-Prot, Gene Ontology (GO), Clusters of Orthologous Groups of proteins (KOG/COG/eggNOG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases using BLASTX to identify the proteins. The DESeq R package (1.10.1) was used to provide statistical routines for determining differential expression. Genes with adjusting by the Benjamini and Hochberg approach, which P-value < 0.05 were assigned as differentially expressed. The KOBAS software was used to test the statistical enrichment of differential expression genes in KEGG pathways 55 . The Gene Set Enrichment Analysis (GSEA) was using to show the variability of DESeq clursters within KEGG pathway 56 between the combination as NB3 vs CK3, NB3 vs Ld3, NB3 vs Ld6, CK3 vs Ld3, CK3 vs Ld6, Ld3 vs Ld6. The results of GESA were visualized with Cytoscape. Metabolite extraction and analysis Each group has six biological replicates, and the samples were prepared with following steps. 400 µL of iced Methanol/Acetonitrile (1: 1, v: v)(rank of LC-MS, CNW Technologies) was added into 100µL sample in 4°C and vortexed for 30sec, at − 20°C incubated for 20min, centrifuged at 14,000 rpm for 15 min at 4°C. Supernatant was transferred to a new tube and dried in a vacuum concentrator than using 100 µL of Acetonitrile/Water (1: 1, v: v) (rank of LC-MS, CNW Technologies) to reconstitute. 60µL aliquot of the supernatant was used to analysis via UHPLC-QTOF-MS. The LC-MS/MS analyses were performed using 1290 UHPLC system (Agilent Technologies) with ACQUITY UPLC BEH amide column (1.7µm, 2.1 mm × 100 mm, Waters) coupled to a Triple TOF 5600 (Q-TOF, AB Sciex) instrument 57 . Analyst TF 1.7 software (AB Sciex) which was used to control the AB5600 TripleTOF(AB Sciex) continuously evaluates the full scan-surveyed MS data. And the mobile phase consisted of A and B which was passed through the elution gradient as 0 min, 95%B; 0.5 min, 95%B; 7 min, 65%B; 8 min, 40%B; 9 min, 40%B; 9.1 min, 95%B; and 12 min, 95% B, which was delivered at 500µL/min, and the injection volume was 2µL. A was 25mM Ammonium acelate (rank of LC-MS, CNW Technologies) and 25mM Ammonium hydroxide (rank of LC-MS, CNW Technologies) in water (pH = 9.75), and B was Acetonitrile (rank of LC-MS, CNW Technologies). The electrospray ionization (ESI) source conditions were as follows: ion source gas 1 as 60psi; ion source gas 2 as 60; curtain gas as 30; source temperature of 550°C; and ion spray voltage floating (ISVF) at 5000 V or -4000 V in positive or negative mode, respectively. By using the SIMCA14 software package (Umetrics, Umea, Sweden), PCA (principal component analysis) and OPLS-DA (orthogonal projections to latent structures–discriminate analysis) were implemented by with the results including peak numbers, sample names, and normalized peak areas. OPLS-DA was used to identify significantly different metabolites between the two comparison groups. The VIP values (variable importance for the projection values) were obtained to clarify the analysis, which exceeding 1.0 was first selected as different metabolites. Student’s T test was used to evaluate the remaining variables. The variables between groups were discarded with P > 0.05. And each metabolite’s FC value (fold change value) was calculated by comparing the mean value of the peak area. The KEGG Online databases were used to search relate pathways, and differential metabolites were cross-linked to KEGG pathways. Integrative analysis of metabolome and transcriptome The PCC (Pearson correlation coefficients) and CCA (canonical correlation analysis) were used to assess the integration of the metabolome and transcriptome. Transcriptome and metabolome datasets were combined to create a general metabolite-transcript network centred on genes according to the KEGG identification. The results of KEGG identification were visualized with Cytoscape. Declarations Acknowledgments We thank Professor Liang-jian Qu from Chinese Academy of Forestry, Beijing, China for generously providing gypsy moth eggs. This study was supported by NSFC (No. 31670659). Competing interests The authors declare no competing interests. References Robert, Poulin., Fanny Maure.. Host Manipulation by Parasites: A Look Back Before Moving Forward. Trends in Parasitology 31(11), 563-570 doi: 10.1016/j.pt.2015.07.002 (2015) Biron, D.G., Ponton, F.L., Marché, G.N., Thomas, F. 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Physiological Reviews, 93(3), 1019-137. doi: 10.1152/physrev.00028.2012 (2013) Mazzon, M., Castro, C., Thaa, B., Liu, L., Mutso, M.. Alphavirus-induced hyperactivation of PI3K/AKT directs pro-viral metabolic changes. PLoS Pathogens , 14(1), e1006835. doi:10.1073/pnas.0409457102 (2018) Grabherr, M.G., Haas, B.J., Yassour, M., Levin, J.Z., Thompson, D.A.. Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nature Biotechnology , 29(7), 644-52. doi:10.1038/nbt.1883 (2011) Kanehisa, M., Goto, S., Kawashima, S., Okuno, Y., Hattori, M.. The KEGG resource for deciphering the genome. Nucleic Acids Research , 32, D277-80. doi:10.1093/nar/gkh063 (2004) Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L.. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences, 102(43), 15545-50. doi:10.1073/pnas.0506580102 (2005) Ivanisevic, J., Elias, D., Deguchi, H., Averell, P.M., Kurczy, M.. Arteriovenous Blood Metabolomics: A Readout of Intra-Tissue Metabostasis. Scientific Reports, 5, 12757. doi:10.1038/srep12757 (2015) Tables Table. 1 Amount of Annotated Metabolins in KEGG Databases of Positive Mode and Negative Mode Group Different Number (POS) Up-regulated Number (POS) Down-regulated Number (POS) Different KEGG Number (POS) Different Number (NEG) Up-regulated Number(NEG) Down-regulated Number(NEG) Different KEGG Number (NEG) NB3 vs CK 538 274 264 51 515 191 324 37 NB3 vs Ld3 871 374 495 81 906 362 544 73 NB3 vs Ld6 865 431 434 71 870 288 582 73 Ld3 vs Ld6 494 291 203 44 562 236 326 44 CK3 vs Ld3 605 258 347 71 752 336 416 71 Table. 2 KEGG Enrichment Pathways between Two Groups by Integrative Analysis of Metabolome and Transcriptome Name of KEGG Pathway Positive Mode Negative Mode NB3vsCK3 NB3vsLd3 NB3vsLd6 Ld3vsLd6 CK3vsLd3 NB3vsCK3 NB3vsLd3 NB3vsLd6 Ld3vsLd6 CK3vsLd3 Citrate cycle (TCA cycle) non non non non non 2 7 14 non 2 Pentose phosphate pathway non non non non non non 9 7 2 2 Pentose and glucuronate interconversions non non non non non non 4 24 non non Fructose and mannose metabolism non non non non non non 12 12 non 2 Galactose metabolism non 17 13 8 16 non 17 17 3 15 Ascorbate and aldarate metabolism non 16 non non 6 non 17 19 2 4 Fatty acid biosynthesis non non 11 2 non non 15 non 4 9 Fatty acid elongation non 2 non non non non 5 non 2 2 Fatty acid degradation 3 2 non non non non 4 non non 5 Steroid biosynthesis non non non non non non 3 non non 2 Ubiquinone and other terpenoid-quinone biosynthesis 3 4 non non non 4 5 non non non Oxidative phosphorylation non non non non non non 5 non non non Arginine biosynthesis 6 5 non 6 6 non 5 10 non 4 Purine metabolism 3 non 35 11 7 12 28 31 14 13 Caffeine metabolism non 3 non non 2 non non non non non Pyrimidine metabolism 4 9 15 8 5 non 9 15 7 4 Alanine, aspartate and glutamate metabolism 6 non non 6 3 2 16 19 4 5 Glycine, serine and threonine metabolism 2 non 14 non 14 non non non non 2 Cysteine and methionine metabolism 2 13 16 non 9 4 11 non 3 8 Valine, leucine and isoleucine degradation non non non non non non non 10 non 5 Valine, leucine and isoleucine biosynthesis non non non 2 non non non 5 4 non Lysine degradation 5 11 non 5 8 4 11 13 3 8 Arginine and proline metabolism 7 15 12 6 4 2 non 12 non non Histidine metabolism 2 non non non 2 non non 5 non non Tyrosine metabolism 8 12 10 2 7 8 12 10 non non Phenylalanine metabolism 6 11 8 non 4 7 13 10 non 4 Tryptophan metabolism 5 14 13 non 11 non non non non non Phenylalanine, tyrosine and tryptophan biosynthesis 3 non non non 2 2 non non non 2 beta-Alanine metabolism non 9 9 non non 2 non non 4 non Taurine and hypotaurine metabolism 4 non non 3 non 4 non 8 non non D-Glutamine and D-glutamate metabolism non non non 2 non non non non non non Glutathione metabolism 8 non 22 4 9 5 non 23 non 5 Starch and sucrose metabolism non non non non 7 non 19 20 non 9 Amino sugar and nucleotide sugar metabolism 3 20 16 3 10 non non 16 non 11 Glycerolipid metabolism non non non non non non non non non 10 Inositol phosphate metabolism non non non non non non non non 3 3 Glycerophospholipid metabolism 6 18 24 5 10 non 15 21 4 4 Arachidonic acid metabolism 2 non non non non non non non non non alpha-Linolenic acid metabolism 2 4 non non 2 2 non non non 2 Pyruvate metabolism non non non non non non 20 14 non non Glyoxylate and dicarboxylate metabolism 3 non non 5 6 6 10 14 non 8 Propanoate metabolism 3 non non non non non non non non non Butanoate metabolism 3 non non 2 non non non 6 non non One carbon pool by folate non non non non non non non non 2 non Nicotinate and nicotinamide metabolism non non non 3 non non non non 3 non Pantothenate and CoA biosynthesis non non 4 non non non non non 3 non Folate biosynthesis non 9 9 2 non non non non non 4 Porphyrin and chlorophyll metabolism 2 non non 2 6 non non non non non Nitrogen metabolism 4 non non 5 non non non 7 non 2 Aminoacyl-tRNA biosynthesis non 8 6 non 10 non 10 8 non 12 Biosynthesis of unsaturated fatty acids non non 9 non non 4 5 12 3 9 Carbon metabolism 9 non non 6 8 8 20 27 2 13 2-Oxocarboxylic acid metabolism 3 10 8 non 8 4 13 19 non 10 Fatty acid metabolism non non non 2 non non non non 2 5 Biosynthesis of amino acids 18 25 30 12 26 15 25 36 11 27 ABC transporters 7 18 14 8 13 non 14 15 6 12 FoxO signaling pathway non non non 6 non non non non non non Phosphatidylinositol signaling system non non non 2 non non 10 non 5 5 Neuroactive ligand-receptor interaction 2 8 non 4 4 non non 11 non 2 mTOR signaling pathway 2 non non non non non non non non non Protein digestion and absorption 4 8 non non non 2 8 non non non Bile secretion 3 non 6 non non non non 6 non non Parkinson disease 3 non non non non 2 non non non non Alcoholism non non non non non 2 non non non non TOTAL （ amount of covering pathways ） 155(35) 271(25) 314(22) 132(28) 225(29) 103(22) 375(32) 475(34) 96(23) 251(38) Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-414994","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":22017956,"identity":"e9fb7bbb-011b-4ced-9322-39158bbf3283","order_by":0,"name":"Fengjiao Li","email":"","orcid":"","institution":"Northwest A\u0026F University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fengjiao","middleName":"","lastName":"Li","suffix":""},{"id":22017958,"identity":"11817b93-78a9-4e4e-ac40-04daecc991a9","order_by":1,"name":"Yajie Wang","email":"","orcid":"","institution":"Northwest A\u0026F University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yajie","middleName":"","lastName":"Wang","suffix":""},{"id":22017960,"identity":"5ae832ae-3e39-45ab-8230-7e8bf40d6632","order_by":2,"name":"Xiao Yu","email":"","orcid":"","institution":"Northwest A\u0026F University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiao","middleName":"","lastName":"Yu","suffix":""},{"id":22017961,"identity":"df53dcab-3e99-49be-abc7-6fbb087f39ca","order_by":3,"name":"Dun Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/UlEQVRIiWNgGAWjYJACZiBmbGBvAHP4gdiASC08B8AcyQbitUgkEKnF4PjZw68Lau7I9ku+PSb5s81OgoG9eZsEQ80d3FrO5KVZzzj2zHjm7Lw0ad62ZAkGnmNlEgzHnuHUYnYgx8yYh+1w4obbOWa3GduY6xgkcswkGBsO49Zy/g1Qy7/DiftvnjG7+bOtXoJB/g0BLTdyjB/ztgFtkeAxuwFkSDAAGXi12N94Y8bM23fYeMaZHPPfPOeOS7DxpBVbJBzDrUWyP8f4M8+3w7L97WeMDX+UVUvwsx/eeONDDW4tQMAmgcoFEQn4NABj8gN++VEwCkbBKBjxAACG+lVZSBgEJQAAAABJRU5ErkJggg==","orcid":"","institution":"Northwest A\u0026F University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Dun","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2021-04-12 15:14:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-414994/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-414994/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":8238931,"identity":"39784528-757e-40ef-bbd2-fe9db1f5fde5","added_by":"auto","created_at":"2021-04-20 18:17:59","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":78076,"visible":true,"origin":"","legend":"Pathway Enrichment Statistic of the DEGs of KEGG Database \n(A) Cluster Analysis of all the samples The horizontal ordinate represents all samples, and the vertical ordinate represents the logarithm of component. (B) Stacking Bar Chart of the Different Metabolites (C-G) The top 20 annotated KEGG pathways in different groups was statistic to show the enrichment. The horizontal ordinate represents the rich factors, and the vertical ordinate represents the top 20 annotated KEGG pathways. (C) NB3 versus CK3, (D) NB3 versus Ld3, (E) NB3 versus Ld6, (F) Ld3 versus Ld6, (G) CK3 versus Ld3.\nC: NB3 versus CK3, D: NB3 versus Ld3, E: NB3 versus Ld6, F: Ld3 versus Ld6, G: CK3 versus Ld3.\n","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-414994/v1/558e033a1005480a8f84a0e5.jpg"},{"id":8238935,"identity":"695a3153-7a38-451a-921a-0b8f956e8b0b","added_by":"auto","created_at":"2021-04-20 18:17:59","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":85666,"visible":true,"origin":"","legend":"Enrichment Map visualization of the GSEA results.\nThe nodes represent for the pathways enriched by GO and KEGG term. The node size is proportional to genes amount in pathway. The node color stands for the normalized enrichment scores (NES), and filtrating criteria of nodes were FDR\u003c0.25 and P\u003c0.05, as illustrated in figure legend. The edges thickness stands for the extent of genes sharing between nodes. \n(A)\tNB3 versus CK3, (B) NB3 versus Ld3, (C) NB3 versus Ld6, (D) Ld3 versus Ld6, (E) CK3 versus Ld3.\n","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-414994/v1/b45839f09899272ad34c4403.jpg"},{"id":8239117,"identity":"e91b5971-074f-43c5-95ff-0d59481df64b","added_by":"auto","created_at":"2021-04-20 18:20:59","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":94465,"visible":true,"origin":"","legend":"Analysis of the Different Metabolites\n(A-B) Cluster Analysis of all the samples The horizontal ordinate represents all samples, and the vertical ordinate represents the logarithm of component. (A) Positive mode. (B) Negitive mode. (C-D) Venn diagram of Different Metabolins (C) Positive mode D: Negtive mode. (E-F) Stacking Bar Chart of the Different Metabolites (E) Positive mode F: Negtive mode. (G-P) Pathway Enrichment Statistic of the Different Metabolites of KEGG Database The top 20 annotated KEGG pathways in different groups was statistic to show the enrichment. The horizontal ordinate represents the rich factors, and the vertical ordinate represents the top 20 annotated KEGG pathways (G) NB3 versus CK3 in positive mode, (H) NB3 versus CK3 in negitive mode, (I) NB3 versus Ld3 in positive mode, (J) NB3 versus Ld3 in negitive mode, (K) NB3 versus Ld6 in positive mode, (L) NB3 versus Ld6 in negitive mode, (M) Ld3 versus Ld6 in positive mode, (N) Ld3 versus Ld6 in negitive mode, (O) CK3 versus Ld6 in positive mode, (P) CK3 versus Ld6 in negitive mode.\n","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-414994/v1/1ecdb1708c5823b36201c48a.jpg"},{"id":8238933,"identity":"c95ed2f7-c9dc-4563-b546-592567f80f0e","added_by":"auto","created_at":"2021-04-20 18:17:59","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":203240,"visible":true,"origin":"","legend":"Integrative Analysis of Metabolome and Transcriptome\n(A-B) Venn diagram of Different Expression Genes and Metabolins (A) Positive mode (B) Negtive mode. (C) Stacking Bar Chart of the Different Expression Genes and Metabolites (D-E) Pathway Statistic of the Different Expression Genes and Metabolites (D) Positive mode (E) Negtive mode. (F) Enrichment Map visualization of the Different Expression Genes and Metabolites\n","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-414994/v1/28102d1a25c235b5866798fb.jpg"},{"id":15673422,"identity":"4ee9f59d-16c6-4f93-9f1a-af53592f4b83","added_by":"auto","created_at":"2021-11-18 14:17:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":607568,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-414994/v1/d2cbd307-274f-4f06-9702-1503e6d545e0.pdf"},{"id":8239118,"identity":"130de159-439a-4be1-8286-a50cf9f1e25d","added_by":"auto","created_at":"2021-04-20 18:20:59","extension":"doc","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2478080,"visible":true,"origin":"","legend":"","description":"","filename":"20210412Supportinginformation.doc","url":"https://assets-eu.researchsquare.com/files/rs-414994/v1/e9d37a0ca27dfa31cf7d47a7.doc"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eIntegrated Transcriptomic and Metabolomic Analysis of \u003cem\u003eLymantria dispar \u003c/em\u003emultiple nucleopolyhedrovirus (LdMNPV) infected \u003cem\u003eLymantria dispar\u003c/em\u003e in Tree-top Disease\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn various parasites, host manipulating in protein transcription and expression, cellular metabolism, signal transduction and even behavior is substantive phenomenon, which is benefited to increase fecundity and transmission rates \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. The baculoviruses provide an example of parasite-induced host manipulation, by which infection resulting in a series of obvious behavior change in the hosts.\u003c/p\u003e\n\u003cp\u003eIn retrospect, the intriguing phenomenon was first recorded in 1891 and was named \u0026ldquo;Tree Top Disease\u0026rdquo; or \u0026ldquo;Wipfelkrankheit\u0026rdquo; by Hofmann\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Till the late 1940s, it was confirmed the diseases causing by virus\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Baculoviruses are classified as a family of large rod-shaped circular double-stand DNA viruses, which specifically infect arthropods and have a unique replication\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Relying on the adaption for insect growth pattern and life cycle, the baculoviuses acquired a biphasic replication cycles, which including two individual virion phenotypes, the occlusion derived viruse (ODV) and the budded viruse (BV)\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. The two viral forms, being genetically identical but morphologically different, preformed a synergistic action, giving expression to functions in both cell-to-cell (BV) and insect-to-insect (ODV) transmission, and also benefited for increasing efficiency of infection and virus titer\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. On the other hand, the unique replication model causing the interaction mechanism between virus and host was time-ordered, dynamic and complicated, which hardly to be revealed.\u003c/p\u003e\n\u003cp\u003eBaculoviruses lead typically abnormal behaviors on scheduling, which including increasing food intake, ELA, extended instar duration and climbing to elevated location before death\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. As nonliving entity, virus needs to manipulate host cell program upon successfully infecting to survival and repilication. The effects of parasitifer infection were shown as behavior change in macroscopic aspect, which leading by manipulation of signaling transduction and alteration of cellular metabolism in microscopic aspect. The Enhanced Locomotory Activity (ELA) is typical early sign of baculoviruses infection\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. In 3rd-instar \u003cem\u003eLymantria dispar\u003c/em\u003e larvae, the ELA was documented as appearing at average of 3.75 days post infection (dpi) and the phenomenon dying out at average of 4.75 dpi \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. With systemic infection further expanding, ELA was the typical description of usurping caterpillar behavior, which normally occurred at healthy larval last instar and was administered by codeterminantion of larval physiological indexs like body size, hormone, phototaxis and geotaxis\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. It is reported that in \u003cem\u003eBombyx mori\u003c/em\u003e the hormone metabolism manipulation is important to virus leading ELA\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. The virus-induced climbing behavior also was refereed to such physiological alterations as geotaxis, phototaxis, vision, olfaction and rhythm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Strinkly, the virus-induced climbing behavior happens in terminal, when the virus vastly replicating at all tissues, but the sick larvae still keep strong climbing ability. Goulson et al was hypothesized that the climbing behavior might be driven by sick larvae to get behavioral fever to respond to infection\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Investigations have suggested that the protein tyrosine phosphatase (\u003cem\u003eptp\u003c/em\u003e) gene is required for inducing the climbing behaviors in Group I Alphabaculovirus, including \u003cem\u003ebombyx mori\u003c/em\u003e Nucleopolyhedrovirus(BmNPV) and AcMNPV \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. In 2011, Hoover et al. reported that the ecdysteroid uridine 5\u0026rsquo;-diphosphate (UDP)-glucosyltransferase (\u003cem\u003eegt\u003c/em\u003e) gene of LdMNPV was necessary to trigger the host behavior changes\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Similarly, the \u003cem\u003eegt\u003c/em\u003e gene of \u003cem\u003eSpodoptera exigua\u003c/em\u003e Multiple embedded Nucleopolyhedrovirus(SeMNPV) has been confirmed to have the same effect in hyperactivity and virus-induced climbing behavior \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. By analyzing the transcriptome of silkworm larvae brains, it was reported that BmNPV-induced hyperactive behaviors were related to circadian rhythms, synaptic transmission and the serotonin receptor signal pathway\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Baculovirus were described to be equipped with photolyase-like genes, which have circadian clock regulation function and the UV-induced DNA repair activity\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Previous study was revealed that in LdMNPV-infected hyperactived larvae the photosensitivity was remarkably increased and the rhythmicity relevant genes, especially \u003cem\u003eper\u003c/em\u003e and \u003cem\u003etim\u003c/em\u003e, was violently impacted\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. The phenomenona occurring in host may operate by more complicated interaction as gene expression change, hormone regulation and metabolism alteration, which created by competition of control between parasite and host\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. However, the mechanism by which NPV leading behavior changes is unclear.\u003c/p\u003e\n\u003cp\u003eIn the current study, based on the biphasic life pattern of virus and experience of larvae behavior alteration, four different time points were selected for the integrated analysis of transcriptomic and metabolomic comparison to be carried out. In order to reveal interactions between LdMNPV and \u003cem\u003eLymantria dispar\u003c/em\u003e and the interaction changes in chosen time points.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003cp\u003e\u003cstrong\u003eTranscriptome sequencing and data analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBefore the analysis of transcriptome and metabolome, we drew the survival curve in LD90 (Lethal Dose, 90%) LdMNPV-infected and the result shown in Supplemental Figure S1. The curve shown two turning points in 72 and 144 hours post infenction (hpi). It is reported that the primary infection usually proceeded between 24 and 48 hpi, and the system infection occurred at later than 72 hpi\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Refer to infected larvae behavior change, LdMNPV biphasic infection mode and inflection points of survival curve are considered together, the 72 and 144 hpi (3 and 6 dpi) were chosen for analysis. Totally, we choose four time points as the newborn 3th-instar larvae (NB3), 72 hours 3th-instar larvae post mock-infected (CK3), 72 hours 3th-instar larvae post infected (Ld3) and 144 hours 3th-instar larvae post infected (Ld6). The chosen time point NB3 as starting point to afford contral and reference. The chosen time point Ld3 (3 dpi) indicate the progress of systemic infection, extensively intruded other organizations and massive replication. And the chosen time point Ld6 (6 dpi) indicated the infection larvaes were faced with imminent death. Because of the mock-infected larvae molt at 4 days old, we choose the 3 days old mock-infected larvae as contral groups.\u003c/p\u003e\n\u003cp\u003eFour groups (NB3, CK3, Ld3 and Ld6) from twelve samples of \u003cem\u003eL. dispar\u003c/em\u003e larvae transcriptomic sequencing respectively generated 63,602,453, 61,981,656, 60,543,314 and 60,633,947 raw reads, and was produced with an average insert size of 298.98bp. In all libraries more than 93.37% of the sequences had a quality score greater than Q30 (Supplemental Table. S1), which indicates that all libraries obtained high-quality raw reads. After qualities were filtered and de novo assembled, the clean reads were totally assembled into 56,923 unigenes by Trinity software, which represents 73.78 Gb of the transcription data. The average length of the unigenes was 1083.78bp, and the N50 was 1877bp (Supplemental Table S2; Supplemental Fig. S2A).\u003c/p\u003e\n\u003cp\u003eThe functional identity of all unigenes was investigated. Homologous annotation for all unigenes was based on information within the GO, Pfam, Swissporot, KOG, eggNOG, Nr, and KEGG databases. Consequently, 26,562 unigenes were annotated at least in one database (Supplemental Table S3). The box-plot figure of all samples is exhibited in Supplemental Figure S2B, of which the FPKM (Fragments Per Kilobase of transcript per Million mapped reads) was used to describe the degree of discretization as evaluation criteria of the gene expression level. The Pearson correlation between the groups is an important parameter, which reflects the experimental reliability and indicates whether the sample selection is reasonable or not. The Pearson correlation and the correlation plot between two samples are exhibited in Supplemental Figure S2C.\u003c/p\u003e\n\u003cp\u003eBy using the DESeq2 softwave, parameters were set as FDK (false discovery rate)\u0026thinsp;\u0026lt;\u0026thinsp;0.01 and FC (fold change)\u0026thinsp;\u0026ge;\u0026thinsp;2; the unigenes from each of the two groups were compared to acquire the different expression genes (DEGs). The results list in Supplemental Table S4. The Cluster analysis was shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eA. It is indicated that the CK3, Ld3 and Ld6 were grouped together and separated with NB3, and the CK3 and Ld3 were similary than others groups also reveal the difference in infection proceeding. The MA-plot (Supplemental Fig. S3A-E) clearly reveals the overall distribution of gene expression levels and fold changes. And the results of MA-plot indicated that the unchanged genes distribution in Ld3 versus Ld6 was exhibited in fusiform, which was different with other groups. Based on the gene expression in the different samples, to identify the annotation of DEGs function, the number of annotated DEGs in different databases is listed as in Supplemental Table S5.\u003c/p\u003e\n\u003cp\u003eIn GO annotations, these unigenes were divided into 53 categories belonging to biological processes, cellular components and molecular functions. The DEGs were specified to GO categories to determine functional classifications. Related to biological process, most DEGs were involved in metabolic processes, cellular processes, single-organism processes, biological regulation, localization and response to stimulus. In the cellular component, the DEGs were involved in cells, cell parts, membranes, membrane parts and extracellular regions. In molecular functions, most GO terms concentrated upon binding and catalytic activity. The results of GO database annotated DEGs between groups were shown in Supplement Figure S4.\u003c/p\u003e\n\u003cp\u003eIn KEGG annotations, a total of 10,157 unigenes were mapped onto 303 different KEGG pathways found in human diseases, genetic information processing, metabolism, organismal systems, environmental information processing and cellular processes in six categories. The stacking bar chart of DEGs was shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eB. In general, in NB3 versus CK3 and Ld3 versus Ld6, the number of up regulation DEGs is more than down, and the amount of DEGs is smallest in Ld3 versus Ld6. It is also indicated that the immune system was not obviously activate in infection larvae, but Signal transduction, Xenobiotics biodegradation and metabolism, Carbohydrate metabolism and Lipid metabolism were significant enriched. Additionally, Replication and repair and Folding, sorting and degradation were drastic change with infection process. The Supplemental Table S6 list out the top 3 of drastic changed, up-regulated and down-regulated pathways, which were annotated between groups. And the bubble diagrams of pathway enrichment are shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eC-\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eG. According to that, we summarized that between two un-infection groups, NB3 versus CK3, the DEGs mainly enriched in small bioactive molecule metabolism like vitamin and cofactor, the extracellular matrix (ECM)-receptor interaction and the defense to external environment. The two compares, NB3 with Ld3 and NB3 with Ld6, mostly give expression to carbon and amino acid metabolism. Between Ld3 and Ld6, the DEGs enrichment pathways tend to focus on cell supporting in material. Especially the carbon metabolism pathway and biosynthesis of amino acids pathway both were drastic down regulated. But the glycosphingolipid biosynthesis pathway was increased. In CK3 versus Ld3, the enriched pathways involved ribosome cytochrome P450 and energy metabolism, which implicates alteration provide the condition of viral genome replication and satisfy the energy supply.\u003c/p\u003e\n\u003cp\u003eFurthermore, the DEGs were compared with the COG database(Cluster of Orthologous Groups of proteins)and resulted in 26 different functional categories (Supplemental Fig. S5). The DEGs also were annotated to the eggNOG database in different functional categories (Supplemental Fig. S6). Each of them provides panoramic account DEGs between groups from different angles.\u003c/p\u003e\n\u003cp\u003eComparing with the DEGs annotations, the GSEA emphasizes the gene, which plays an important biological effect but only have a subtle change of expression, by enrichment the gene sets. The GESA result, which visualization by Cytoscape, was shown in Figure (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA-\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eE). The topological structure describes the correlation characteristic of gene set, which combines the Jaccard similarity coefficient standard by distance and the overlap coefficient standard by green line. To separate different patterns, we pained the nodes background as violet represents metabolism, aqua represents genetic information processing, and pink represents environmental information processing. Generally, it is shown that in combination as NB3 versus Ld3 and NB3 versus Ld6 the enriched gene sets are numerous in quantity, means larger variations in these two groups. Between NB3 and CK3, the enriched gene sets involved material metabolism and surroundings signal receptor, like phototransduction-fly and neuroactive ligand-receptor interaction, reflecting the larval physiological change of growing process. In the combination as NB3 versus Ld3 and NB3 versus Ld6 the associating gene sets, most of which present an up-regulated trend, mainly included cellular nutrition utilization, energy metabolism and material metabolism, which is shown as complicated network painted in violet background. In this two comparison, the up-regulated gene sets were peroxisome, phototransduction-fly and insect hormone biosynthesis, the down-regulated gene sets were lysosome, apoptosis, proteasome, ubiquitin-mediated proteolysis, endocytosis regulation of autophagy, dorso ventral axis formation, protein export and ABC transporters. Compared with the group NB3 versus Ld3, the trend of group NB3 versus Ld6 enriched gene sets integrally appears down-regulation and the scanty up-regulated gene sets focused on energy and material metabolism. As the infection progresses further, it is revealed that in Ld3 versus Ld6 the alteration mainly consists of material metabolism and protein export, especially in fatty acid metabolism. Other gene sets were peroxisome, protein export and neuroactive ligand-receptor interaction. And the down-regulation emphasized the apoptosis. Between CK3 and Ld3, only the Citrate cycle (TCA cycle) and tyrosine metabolism showed the up-regulation. The down-regulated gene sets covered maintenance and development signal and genetic information processing. The decreasing extensively pathways of host genetic information processing accords with the viral manipulation in early replication.\u003c/p\u003e\n\u003cp\u003eThe transcriptomic analysis shown that after being infected, the metabolism, signal transductions and detoxication relevant metabolism of \u003cem\u003eL. dispar\u003c/em\u003e larvae were visibly affected, but immune function relevant pathways, like the JAK/STAT signaling pathway, NF/kB signaling pathway and Toll-like Receptors pathway, were not significantly affected. Further more, with infection progressing, the apoptosis was continuous down-regulation.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003cp\u003e\u003cstrong\u003eMetabolite extraction and analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOther than protein-interaction, metabolism is constituted by chemical reactions, which is described metabolites as nodes and functional proteins as edges. Metabolomic analysis of twenty-four samples from four groups (NB3, CK3, Ld3 and Ld6) of \u003cem\u003eL. dispar\u003c/em\u003e larvae was performed via UHPLC-QTOF-MS. As a result, 1,930 and 1,831 metabolins were respectively obtained using POS and NEG mode detection. Based on the PCA Analysis (Supplement Fig. S7) and Cluster Analysis (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA-B), the qualified metabolite data was subjected to differential analysis. After the metabolites were detected by the qualitative analysis, the quantities were compared between groups to show the extent the metabolites changed. The standard P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 of Student's T tests and VIP-values\u0026thinsp;\u0026gt;\u0026thinsp;2 of OPLS-DA were used to screen the different metabolites. The amount of different metabolites between groups was shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. To shown the variability we clustered the different metabolins, the result was shown in Supplemental Figure S8. And the Wayne diagram exhibits in all groups the relationship of the change in metabolites (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eC-D). Taken together, the results reflected that in all comparatives the metabolite changes in NB3 versus CK3 and Ld3 versus Ld6 were easement, but in CK3 versus Ld3 was fierce.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cp\u003eTo identify the pathways of metabolites involved, a total of 1,359 metabolites in the POS mode and 1,341 metabolites in the NEG mode were mapped to KEGG metabolic pathways; in POS and NEG mode, the stacking bar charts of different metabolites in KEGG enrichment were shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eE-F; the details are listed in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e; and the bubble diagram of different metabolites in KEGG enrichment were shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eG-P. The stacking bar charts were shown that LdMNPV leading a largescale alteration in metabolism and organismal systems of infected larvae. The results revealed that the different metabolites annotated into KEGG database were concentrated in some key pathways. Generally, in POS mode, metabolic pathway, ABC-transporters and biosynthesis of amino acid were indicated to undergo a violent change in all comparisons. An exception to the above is that protein digestion and absorption emerged in NB3 versus CK3, NB3 versus Ld3,Ld3 versus Ld6, and CK3 versus Ld3. Meanwhile in NB3 versus Ld6, it is shown as glycerophospholipid metabolism. In NEG mode, metabolic pathway, biosynthesis of amino acid, 2-Oxocarboxylic acid metabolism and ABC-transporters were indicated to a violent change in all comparisons. An exception to above, the central carbon metabolism in cancer emerged in NB3 versus Ld3, NB3 versus Ld6 and CK3 versus Ld3; the protein digestion and absorption emerged in NB3 versus CK3, Ld3 versus Ld6 and CK3 versus Ld3; moreover in CK3 versus Ld3, it is shown as aminoacyl-tRNA biosynthesis and biosynthesis of unsaturated fatty acids.\u003c/p\u003e\n\u003cp\u003eThe metabolomics analysis has shown that the LdMNPV induced a largescale alteration in cellular metabolism of infected larvae. In normal physiology status, from NB3 to CK3, the different metabolites, which were enriched into metabolism pathways evenly distribute in amino acid, lipids, and other small molecular metabolistes. After be infected, from CK3 to Ld3, the pathways including amino sugar and nucleotide sugar metabolism, biosynthesis of unsaturated fatty acid biotin metabolism, D-glutamine and D-glutamate metabolism, nitrogen metabolism and galactose metabolism were enriched dramatic change. From Ld3 to Ld6, arginine biosynthesis, galactose metabolism, purine metabolism, amino sugar and nucleotide sugar metabolism, fatty acid biosynthesis and galactose metabolism pathways were enriched further change. Though different viruses appear to activate different metabolic altering pattern, the reprogramming of host cell is determinant to viral growth. In this context, it was pertinent to conclude that the alteration in fatty acid synthesis, carbon source utilization and biosynthesis of amino acid was changed to guarantee optimal microenvironment for LdMNPV\u0026rsquo;s replication and spread. Other wise, after infection the GABAergic synapse, cholinergic synapse, doparninergic synapse, glutarnatergic synapse, neuroactive ligand-receptor interaction and phosphatidylinositol signaling system also constant with infection processing, indicating the viral infection may affect on host\u0026rsquo;s nervous and signal transduction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntegrative analysis of metabolome and transcriptome\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003cp\u003eTo explore further dynamic variation of the infection-caused behavior change in \u003cem\u003eL. dispar\u003c/em\u003e, an integrated and detailed analysis was performed on the transcript and metabolic levels. Before screening data, the Pearson correlation coefficient (PCC) and corresponding P-value were used to filtrate the data simultaneously, with values set to PCC\u0026thinsp;\u0026gt;\u0026thinsp;0.80 and PCCP\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\n\u003cp\u003eTotally, the integrative analysis of metabolome and transcriptome screens 52 pathways in the POS mode and 56 pathways in the NEG mode. The amount of different expression genes and metabolites in KEGG pathway was list on Table. 2. The Wayne diagram exhibits in all groups the relationship of the change in covering KEGG pathways (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eA-B). The stacking bar charts of different expression genes and metabolites in KEGG classification in POS and NEG mode were shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eC and corresponding quantity of different expression genes and metabolites in each KEGG classification were shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eD-E. The results showed that in POS mode the specific differences in NB3 versus CK3 and Ld3 versus Ld6 are covering more KEGG pathways than other compares, but in NEG mode it have more similarity. In general, Global and overview maps, Carbohydrate metabolism and Amino acid metabolism present significant difference in both of POS and NEG mode, but the amount of difference expression genes and metabolites in Ld3 versus Ld6 were smaller than others, especially the CK3 versus Ld3. Strikingly, the difference of energy metabolism were appeared at POS mode in NB3 versus CK3 and Ld3 versus Ld6, and at NEG mode in NB3 versus Ld3, NB3 versus Ld6 and CK3 versus Ld3.\u003c/p\u003e\n\u003cp\u003eThe interaction and enrichment frequency of covering KEGG pathways were visualized in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eF to dig out more details. The figure showed that Carbohydrate metabolism, Amino acid metabolism and Lipid metabolism were enriched to most pathways, as Carbohydrate metabolism have 15 pathways, Amino acid metabolism have 14 pathways, and Lipid metabolism have 11 pathways. The KEGG classifications of Global and overview maps and Nucleotide metabolism were violently fluctuation. What\u0026rsquo;s more, the Alanine, aspartate and glutamate metabolism pathway, Lysine degradation pathway and Tyrosine metabolism pathway in Amino acid metabolism, Glycerophospholipid metabolism pathway in Lipid metabolism, ABC transporters pathway in Translation and neuroactive ligand-receptor interaction pathway in Membrane transport were also drastic fluctuation. Further analysis showed that the specific enriched KEGG pathways were arachidonic acid metabolism, propanoate metabolism, mTOR signaling pathway, parkinson disease and alcoholism in NB3 versus CK3; oxidative phosphorylation in NB3 versus Ld3; D-Glutamine and D-glutamate metabolism, nicotinate and nicotinamide metabolism, one carbon pool by folate and FoxO signaling pathway in Ld3 versus Ld6; and glycerolipid metabolismin CK3 versus Ld3.\u003c/p\u003e\n\u003cp\u003eExcept the 54 pathways of each metabolism classifications, other enrichment only covered 10 pathways, including aminoacyl-tRNA biosynthesis pathway, ABC transporters pathway, FoxO signaling pathway, phosphatidylinositol signaling system, neuroactive ligand-receptor interaction pathway, mTOR signaling pathway, protein digestion and absorption pathway, bile secretion pathway, parkinson disease pathway and alcoholism pathway. Among them, the ABC transporters pathway only keeps invariant in NB3 versus CK3 in NEG mode, which showed severe change. The aminoacyl-tRNA biosynthesis pathway was enriched in NB3 versus Ld3, NB3 versus Ld6 and CK3 versus Ld3 in both POS and NEG mode. The protein digestion and absorption pathway was enriched in NB3 versus Ld3 and NB3 versus Ld6 in both POS and NEG mode. The bile secretion pathway shows slight variation in NB3 versus CK3 and NB3 versus Ld6 in POS mode, and in NB3 versus Ld6 in NEG mode. The mTOR signaling pathway, parkinson disease and alcoholism were only changed in NB3 versus CK3,and the FoxO signaling pathway was only changed in Ld3 versus Ld6. It is remarkable that the changes of neuroactive ligand-receptor interaction pathway and phosphatidylinositol signaling system pathway, which showed incompatibility in POS and NEG mode. The change of neuroactive ligand-receptor interaction pathway appears at NB3 versus CK3, NB3 versus Ld3, Ld3 versus Ld6 and CK3 versus Ld3 in POS mode, and at NB3 versus Ld6 and CK3 versus Ld3 in NEG mode. And the change of phosphatidylinositol signaling system pathway occurs at CK3 versus Ld3 in POS mode, and at NB3 versus Ld3, Ld3 versus Ld6 and CK3 versus Ld3 in NEG mode. By comparing the different metabolites, it is reveal that in neuroactive ligand-receptor interaction pathway the incompatibility causing by detection of dopamine, acetylcholine, adenosine and trace amine were different in POS and NEG mode, and in phosphatidylinositol signaling system pathway was phosphatidyl-1D-myo-inositol (PI).\u003c/p\u003e\n\u003cp\u003eBased on the interaction of KEGG pathways and dynamic change between each groups, it is filter out that the change of neurotransmitter, cyclohexanehexol and secondary metabolism may associate with host-parasites interaction. The neurotransmitter like dopamine and acetylcholine, increase in NB3 versus CK3 but remain stable in other compares. The caffeine metabolism pathway was enriched in NB3 versus Ld3 and CK3 versus Ld3. In CK3 versus Ld3, the caffeine was increase, and xanthine dehydrogenase/oxidase (XDH) gene was decrease, which relevant to purine metabolism by oxidizing xanthine. In \u003cem\u003eC.elegans\u003c/em\u003e and \u003cem\u003eDrosophila melanogaster\u003c/em\u003e cyclohexanehexol was reported to extend lifespan \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. The inositol phosphate metabolism pathway and phosphatidylinositol signaling system pathway were both enriched in CK3 versus Ld3 and Ld3 versus Ld6, which two pathways link by cyclohexanehexol. In CK3 versus Ld3, the myo-inositol (MI) was increase and PI was decrease. The \u003cem\u003einositol polyphosphate 5-phosphatase\u003c/em\u003e (INPP5A) and \u003cem\u003ephosphatidylinositol-4-phosphate 3-kinase\u003c/em\u003e (PI3K) gene were upregulated and \u003cem\u003einositol 1,4,5-triphosphate receptor\u003c/em\u003e (IP3R) gene was downregulated. And in Ld3 versus Ld6, the PI was increase and MI was decrease. Meanwhile, the \u003cem\u003ephosphatidylinositol-3,4,5-trisphosphate 3-phosphatase\u003c/em\u003e (PTEN/MMAC1), \u003cem\u003emultiple inositol-polyphosphate phosphatase/2,3-bisphosphoglycerate 3-phosphatase\u003c/em\u003e (MINPP1) and \u003cem\u003eip3r\u003c/em\u003e gene were up-regulated, and the \u003cem\u003epi3k\u003c/em\u003e gene was down-regulated. Other metabolisms like pyruvate, N-acetylglucosamine (GluNAc) and NAD\u003csup\u003e+\u003c/sup\u003e also relevant to life prolonging. Among them, only GluNAc was increase, which was enriched in Ld3 versus Ld6. In \u003cem\u003eBombyx mori\u003c/em\u003e, after BmNPV infection the trehalose, malate, fumarate, citrate, succinate, \u0026alpha;-ketoglutarate, phenylalanine and tyrosine showed accumulate in the resistant strain YeA, but in susceptible strain YeB the gluconate, glutamate and aspartate were upregulation \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. The results showed the phenylalanine and tyrosine were kept increasing in CK3 versus Ld3 and Ld3 versus Ld6. In Arginine biosynthesis pathway the different metabolites were glutamine, glutamate and citruline, which show changing consistency. In NB3 versus CK3 this three all decreases, with \u003cem\u003eglutamine synthetase\u003c/em\u003e (GS) gene, \u003cem\u003eglutamate dehydrogenase\u003c/em\u003e (GDH) gene, \u003cem\u003eacylamide amidohydrolase\u003c/em\u003e (ASL) gene and \u003cem\u003eamido acid deacylase\u003c/em\u003e gene were downregulated, and \u003cem\u003eNADPH-diaphorase\u003c/em\u003e gene was upregulated. In CK3 versus Ld3 and Ld3 versus Ld6, the glutamine, glutamate and citruline keep accumulate, but genes expression were altered. In CK3 versus Ld3, \u003cem\u003egs\u003c/em\u003e gene, \u003cem\u003egdh\u003c/em\u003e gene, \u003cem\u003easl\u003c/em\u003e gene and \u003cem\u003earginosuccinate synthetase\u003c/em\u003e (ASS1) gene were upregulated, \u003cem\u003eamido acid deacylase\u003c/em\u003e gene was downregulated. In Ld3 versus Ld6, \u003cem\u003egs\u003c/em\u003e gene, and \u003cem\u003eNAD(P)\u003c/em\u003e\u003csup\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sup\u003e \u003cem\u003eoxidoreductase\u003c/em\u003e gene were upregulated, \u003cem\u003eNADPH-diaphorase\u003c/em\u003e gene was downregulated. Moreover, in Ld3 versus Ld6 glutamate as the principal excitatory amino acid neurotransmitters, accumulate indicate targeted utilization by \u003cem\u003eglutamine synthetase\u003c/em\u003e (GLUL) gene upregulated, which product was glutamine showed increase. And the \u003cem\u003eglutamate decarboxylase\u003c/em\u003e gene was downregulated keeping the content of it product, gamma-Aminobutyric acid (GABA) working as a chief inhibitory neurotransmitter in reducing neuronal excitability, remains stable. The carbohydrate metabolism also revealed noteworthy change after infection. In CK3 versus Ld3, the \u003cem\u003ealpha-D-glucoside glucohydrolase\u003c/em\u003e gene and \u003cem\u003ealpha-D-galactoside galactohydrolase\u003c/em\u003e gene were upregulated, causing accumulate of galactinol, raffinose, sucrose, stachyose, mannose and MI. Than in Ld3 versus Ld6, the expression level of \u003cem\u003ealpha-D-glucoside glucohydrolase\u003c/em\u003e gene and \u003cem\u003ealpha-D-galactoside galactohydrolase\u003c/em\u003e gene remained stable, but the galactinol, raffinose, sucrose, mannose and MI present lack.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eInfection with a wide variety of parasites, including baculovirus, can result in behavior changes in the host. For survival and replication, the parasites have to conquer host defenses barriers of immunity, even manipulate the host\u0026rsquo;s physiology\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Some reports have provided insight into how baculovirus producing influences on host, depending on some core genes or even just one gene\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Within the last decade, the primary host behavior manipulation gene of NPV had been brought to light\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. The details on host reacting and its mechanism to virus-induced activity rarely had been addressed. In this study, through the integrative analysis of metabolome and transcriptome between the key time points, which were chosen by critical moment of replication characteration and infected host larval behavior changes, and we sum up the alteration of MI, PI and relevant genes involved in larval extended instar duration, and the changes of caffeine, glutamate and GABA involved in LdMNPV inducing behavior change.\u003c/p\u003e\n\u003cp\u003eParasites are capable of inducing host behavior alterations in many aspects to increase transmission rates\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. The NPV infection triggered abnormal physiological status, like increasing food intake, ELA, extended instar duration and climbing to elevated location before death foraging\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e, which leading by alteration of host cellular metabolism and manipulation of signaling transduction. The infected \u003cem\u003eL. dispar\u003c/em\u003e larvae had prolonged their 3th instar duration, which was 4 to 5 days in healthy larvae, to 7 to 8 days\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. The survival curve in LD90 of LdMNPV-infection (Supplemental Figure S1) was shown that the 3 and 6 dpi were two inflection points. Baculoviuses specially have a biphasic replication cycle, which including two individual virion phenotypes, the ODV and the BV\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. The ODV and BV were genetically identical but morphologically different, which also were related-time produnction. Combined with the biphasic infections and the early infection mainly happening in midgut which only regional impact, the time point Ld3 and Ld6 were chosen to indicate the proceeding of systemic infection at early and imminent stages of massive replication.\u003c/p\u003e\n\u003cp\u003eIn the four groups (NB3, CK3, Ld3 and Ld6) of \u003cem\u003eL. dispar\u003c/em\u003e larvae, twelve transcriptomic samples were sequenced. On the whole, the CK3 and Ld3 were more similary than others groups (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eA). Based on DEGs annotation, it is showed that the pattern of NB3 versus CK3 and Ld3 versus Ld6 were approximate, and the alteration in cellular mainly concentrates on benefiting virus DNA replication, the energy supply and detoxication relevant metabolism were visibly affected, and immune function relevant pathways, like the JAK/STAT signaling pathway, NF/kB signaling pathway and Toll-like receptors pathway, were not significantly affected (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eB). After being infenction, the DEGs analysis showed regulatory strategy change in different infection stages, involving affect material supply of virion production and anti-apoptosis to prolong infected cell survival. Furthermore, by KEGG annotations, the DEGs enrichment showed that between CK3 and Ld3, the violently upregulated pathways were metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450 and galactose metabolism; and the drastically downregulated pathways were ribosome, carbon metabolism and phagosome, which reveals alteration provide the condition of viral replication, alteration of energy supply and avoid cell damage, toxin and reactive oxygen species (ROS) stress causing by virus repilication. Between Ld3 and Ld6, the violently upregulated pathways were carbon metabolism, phenylalanine metabolism and biosynthesis of amino acids; and the drastically downregulated pathways were lysosome, mTOR signaling pathway and longevity regulating pathway-multiple species. The upregulated of carbon metabolism, phenylalanine metabolism and biosynthesis of amino acids confirmed infection causing globally alteration of material utilization. The downregulated of lysosome, mTOR signaling pathway and longevity regulating pathway were benefit in keeping host cell survival. The genes, which were enrichment in lysosome pathway involving in metabolism disorder, and the upregulated gene could promote glycerolipid collection\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. The drastic changes of longevity regulating pathway may relate to prolonging instar duration of infected larvae. It is also reported that dietary restriction and genetic down-regulation of nutrient-sensing pathways, like Insulin-like signaling pathway and mTOR signaling pathway can substantially increase life span\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eGenerally, the GESA result (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA-E) is shown that NB3 versus Ld3 and NB3 versus Ld6 the gene sets which were enriched in have more volume, reveals the larger variations in these two comparisons. From NB3 to CK3 (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA), the enrichment was involved in material metabolism and surroundings signal receptor, which reflecting the larval physiological change of growing process. Between CK3 and Ld3 (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eE), only the Citrate cycle (TCA cycle) and tyrosine metabolism showed the upregulation, and lots of gene sets downregulated mainly covered maintenance and development signal and genetic information processing, which was accords with the viral manipulation in early replication. The transcriptomic analysis shown that pathways of metabolism, signal transductions and detoxication relevant metabolism were visibly affected in infection \u003cem\u003eL. dispar\u003c/em\u003e larvae. Further more, with the infection proceeding, it is revealed that in Ld3 versus Ld6 (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eD) the alteration mainly consists of material metabolism and protein export, especially in fatty acid metabolism, and the apoptosis was continuous downregulation.\u003c/p\u003e\n\u003cp\u003eTwenty-four metabolomics samples obtained 1,930 metabolins in POS mode and 1,831 metabolins in NEG mode. In contrast between groups, a large variety of metabolites show significant reduction in the virion production stages (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA-B). Results of the amount of different metabolites between groups, the variability of different metabolins and the Wayne diagrams (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eC-F) reflected that the metabolite changes in NB3 versus CK3 and Ld3 versus Ld6 were easement, but in CK3 versus Ld3 was fierce. The metabolin enrichment showed the metabolic pathway, ABC-transporters, 2-Oxocarboxylic acid metabolism, biosynthesis of amino acid and protein digestion and absorption merged to produce a violent change in all comparisons. Meanwhile, the alteration of central carbon metabolism in cancer, which was accredited in lots of human source virus infections, only emerged in NB3 versus Ld3, NB3 versus Ld6 and CK3 versus Ld3. In rapidly replication viruses, the hyper-activation of sustained metabolic pathways was sufficed to increasing viral titers\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. The results of different metabolites KEGG enrichment revealed that the different metabolites were concentrated in some key pathways. From NB3 to CK3, as normal physiology status, the different metabolites have been enriched evenly distribute in amino acid, lipids, and other small molecular metabolistes. After be infected, from CK3 to Ld3, the enriched pathways covering amino sugar and nucleotide sugar metabolism, biosynthesis of unsaturated fatty acid biotin metabolism, D-glutamine and D-glutamate metabolism, nitrogen metabolism and galactose metabolism were enriched dramatic change. The nutrients uptake and utilization alteration tend to provide enough ATP to meet the energy costs of virus DNA replication. The increasing of lipid material was induced by the needed of additional membrane material for the viral particle envelopment. Though different viruses appear to activate different metabolic altering pattern, the reprogramming of host cell is determinant to viral growth. Since Munger et al reporting the first eukaryotic virus tampering cellular metabolomics, different studies shown variously manipulate multiple major metabolic pathways to reprogram host cellular nutrients uptake and utilization to meet the increasing material and energy costs to guarantee the optimal microenvironment\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. The research also shown that the viruses inducing aerobic glycolysis as known as the \u0026ldquo;Warburg effect\u0026rdquo; \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. The alterations of nutrients uptake and utilization could provide ATP in a rapid fashion to meet the high energy costs and avoid cell ROS stress of virus replication, and the increasing of lipids by altering the fatty acid synthesis, is needed to afford the additional membrane material for the viral particle envelopment.\u003c/p\u003e\n\u003cp\u003eIn comprehensive consideration of existing research and the data of transcription and metabolism, more detail about LdMNPV and host interaction was uncovered. The integrative analysis of metabolome and transcriptome totally enriched 52 correlational pathways in the POS mode and 56 correlational pathways in the NEG mode. The results showed that the specific differences in NB3 versus CK3 (physiological status) and Ld3 versus Ld6 were covering more KEGG pathways with less enrichment amount of different express genes and metabolites, between which have more similarity than others compares (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eA-C). The Global and overview maps, Carbohydrate metabolism and Amino acid metabolism present significant difference in both of POS and NEG mode (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eC), but the amount of difference expression genes and metabolites in Ld3 versus Ld6 were smaller than others, especially the CK3 versus Ld3 (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eD-E). Comparing with the normal physiological status, the alteration of infected status refers to signal transduction, nucleotide metabolism, fatty acid metabolism, amino acid metabolism and cofactors metabolism.\u003c/p\u003e\n\u003cp\u003eThe figure.4F and table.2 were showed that Carbohydrate metabolism, Amino acid metabolism and Lipid metabolism were enriched to most pathways, Carbohydrate metabolism have 15 pathways, Amino acid metabolism have 14 pathways, and Lipid metabolism have 11 pathways. In metabolism relevant pathway the dynamic change of the Alanine, aspartate and glutamate metabolism pathway, Lysine degradation pathway and Tyrosine metabolism pathway in Amino acid metabolism, Glycerophospholipid metabolism pathway in Lipid metabolism, ABC transporters pathway in Translation and neuroactive ligand-receptor interaction pathway in Membrane transport were striking. It is showed that the specific enriched KEGG pathways were arachidonic acid metabolism, propanoate metabolism, mTOR signaling pathway, parkinson disease and alcoholism in NB3 versus CK3; oxidative phosphorylation in NB3 versus Ld3; D-Glutamine and D-glutamate metabolism, nicotinate and nicotinamide metabolism, one carbon pool by folate and FoxO signaling pathway in Ld3 versus Ld6; and glycerolipid metabolismin CK3 versus Ld3. For another, the enrichments excepting metabolism relevant only covered 10 pathways, including aminoacyl-tRNA biosynthesis pathway, neuroactive ligand-receptor interaction pathway, ABC transporters pathway, phosphatidylinositol signaling system, FoxO signaling pathway, mTOR signaling pathway, protein digestion and absorption pathway, bile secretion pathway, parkinson disease pathway and alcoholism pathway. Except the aminoacyl-tRNA biosynthesis pathway, neuroactive ligand-receptor interaction pathway, ABC transporters pathway and phosphatidylinositol signaling system, the others just change a few in limited compares. The aminoacyl-tRNA biosynthesis pathway was violent alteration in CK3 versus Ld3, reflecting that the reprogram of host cell transcription preferences which leading by LdMNPV. There have not enrichment any difference in Ld3 versus Ld6, which means alteration of aminoacyl-tRNAs were keeping stable with infection processing. Moreover, it is reported that after infected by BmNPV in \u003cem\u003eBombyx mori\u003c/em\u003e larvae the trehalose, malate, fumarate, citrate, succinate, \u0026alpha;-ketoglutarate, phenylalanine and tyrosine were accumulated in the resistant strain YeA, but in susceptible strain YeB the gluconate, glutamate and aspartate showed upregulation\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. The integrative analysis showed in \u003cem\u003eL. dispar\u003c/em\u003e larvae the phenylalanine, tyrosine, gluconate and glutamate were continued accumulation in CK3 versus Ld3 and Ld3 versus Ld6, which revealed different patterns of host-virus interaction. The gluconate and glutamate were gived further attention, in Ld3 versus Ld6, the accumulation glutamate indicate targeted utilization by \u003cem\u003eglul\u003c/em\u003e gene upregulated leading glutamine showed increase and the \u003cem\u003eglutamate decarboxylase\u003c/em\u003e gene was downregulated causing GABA, a chief inhibitory neurotransmitter, remains stable. In the insect central nervous system (CNS), GABA and glutamate working as antagonists and agonists in neuronal excitability control\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e. It is showed that GABA and glutamate are involved in the mediation of aggressive behavior in invertebrates\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e. In honeybee, the connection between scouting behaviors and catecholamine, glutamate and GABA reflect effects of neurotransmitter to behaviors, and glutamate treatments increased the probability of foragers scouting behaviors\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e. Moreover, in CK3 versus Ld3 the caffeine was increase. It is reasonable to consider that content patterns of caffeine, glutamate and GABA involved in LdMNPV inducing behavior change.\u003c/p\u003e\n\u003cp\u003eMetabolisms like spermidine, pyruvate, GluNAc and NAD\u003csup\u003e+\u003c/sup\u003e were relevanted to life prolonging\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e44\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e. Among them, only GluNAc showed increasing, which was enriched in Ld3 versus Ld6. In \u003cem\u003eC.elegans\u003c/em\u003e and \u003cem\u003eDrosophila melanogaster\u003c/em\u003e cyclohexanehexol was reported to extend lifespan\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e. The inositol phosphate metabolism pathway and phosphatidylinositol signaling system pathway, which linking by cyclohexanehexol, were both enriched after LdMNPV infection. In CK3 versus Ld3, the MI was increase and PI was decrease, and relevent genes, the \u003cem\u003einn5a\u003c/em\u003e and \u003cem\u003epi3k\u003c/em\u003e were upregulated, and \u003cem\u003epi3r\u003c/em\u003e gene was downregulated. And in Ld3 versus Ld6, the PI was increase and MI was decrease, and the \u003cem\u003epten/mmac1\u003c/em\u003e, \u003cem\u003eminpp1\u003c/em\u003e and \u003cem\u003eip3r\u003c/em\u003e gene were upregulated, the \u003cem\u003epi3k\u003c/em\u003e gene was downregulated. As important second messenger, the phosphatidylinositol-3,4,5-triphosphate (PIP3) mediated lots of intracellular signaling molecule which was activating types of growth factors, cellular stimulus or toxic insults and regulates fundamental functions affected transcription, cell cycle progression, proliferation and survival\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e, that keeping stable in all groups. The accumulation of PIP3 in cell will trigger stress resistant and apoptosis. Moreover, intracellular phospholipid signal involved in managing endocytic and exocytic processes, regulating iron channaels, pumps and transporters, coordinating vesicular trafficking and modulating lipid distribution and metabolism\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e. Numbers of pathogens, especially virus, has been recognized reprogram cellular processes by hijack host cell phospholipid signal\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e53\u003c/span\u003e\u003c/sup\u003e. Refer to alteraction of the inositol phosphate metabolism pathway and phosphatidylinositol signaling system pathway in infected larvae, it is hypothesis that MI, PI and relevant genes involving in larval extended instar duration and apoptosis avoiding.\u003c/p\u003e\n\u003cp\u003eConsidering all the results, LdMNPV biphasic infection mode causing host manipulation changes continuously in different time points of infection. Comparing with the normal physiological status, alterations of nutrients uptake and utilization could provide ATP in a rapid fashion to meet the high energy costs and avoid cell stress resistant and apoptosis of virus replication, and the increasing of lipids by altering the fatty acid synthesis, is needed to afford the additional membrane material for the viral particle envelopment, and immune function relevant pathways were not significantly affected. Moreover, maintaining infected cell stability is important to virion production and assembly at terminal of infection and the extended instar duration of host was benefitted to virus production.\u003c/p\u003e\n\u003cp\u003eIn summary, we explored the complicated interactions between LdMNPV and 3th-instar \u003cem\u003eL. dispar\u003c/em\u003e larvae at the metabolome and transcriptome levels, conducted the preliminary analysis, uncovered that the content patterns of caffeine, glutamate and GABA involved in LdMNPV inducing behavior change, and the MI, PI and relevant genes involving in larval extended instar duration and apoptosis avoiding. It is anticipated that further research in relevent pathways will reveal in the complex reactions in conflict between \u003cem\u003eL. dispar\u003c/em\u003e and LdMNPV.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n\u003cp\u003e\u003cstrong\u003eInsect and virus\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eL. dispar\u003c/em\u003e eggs were provided of Professor Liang-Jian Qu from the Chinese Academy of Forestry, Beijing, China. Hatched larvae were raised on artificial diet in a sterile phytotron with conditions as follows: temperature 26\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u0026deg;C, Relative Humidity 60\u0026thinsp;\u0026plusmn;\u0026thinsp;5% and the photoperiod of 14: 10 (Light: Dark).\u003c/p\u003e\n\u003cp\u003eLdMNPV was stored in the laboratory. The ODV s was obtained from inoculated larvae, and prepared by the following steps. Inoculated larvae were washed with 0.25% sodium dodecyl sulfate filtered through filter paper and cheesecloth. Filtrate is washed twice with double-distilled water and centrifuged at 3000rpm for 30mins. The precipitate was re-suspended with double-distilled water and quantified using a bacterial counting chamber, and diluted to the final concentration of 10\u003csup\u003e9\u003c/sup\u003e occlusion bodies (ODVs)/mL. The virus suspensions were stored at 4\u0026deg;C.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003cp\u003e\u003cstrong\u003eSample preparation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNewly molted third-instar larvae were used as the experimental subjects and were randomly divided into two groups: infection group and control group. Larvae of the infection group were fed with 10\u003csup\u003e6\u003c/sup\u003e OBs per larva of LdMNPV. For the control group, the isopyknic double-distilled water was provided using the same method. After having been fed, larvae were reared in a 24-well insect rearing box in individual wells with ample artificial diet in each well. Samples for transcriptome and metabolome analysis were obtained at the newly-molted third-instar larvae (NB3) stage,at 72 hours after treatment for the control group (CK3), at 72 hours after treatment for the LdMNPV infected group (Ld3), and 144 hours after treatment for the LdMNPV infected group (Ld6). The control group did not have any samples at 144 hours after treatment because mock-treated larvae molted into the next instar before 144 hours. Meanwhile༌surplus larvae from each group were kept to confirm the treatment was working. Death for infection was committed by liquefaction, and another group was observed till pupation. Sampled larvae were snap frozen in liquid nitrogen more than 24 hours and stored at \u0026minus;\u0026thinsp;80\u0026deg;C until further steps.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n\u003cp\u003e\u003cstrong\u003eTranscriptome sequencing and data analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTotal RNA was extracted from the intact samples by using TRIzol Reagent (Invitrogen) following the protocol of the manufacturer. Quality of RNA-samples was checked on 1% agarose-gel and the concentration were measured using NanoDrop 2000 (Thermo). Sequencing libraries were generated using NEBNext\u0026reg;Ultra\u0026trade; RNA Library Prep Kit for Illumina\u0026reg; (NEB, USA) and purified by AMPure XP system (Beckman Coulter, Beverly, USA). All cDNA libraries sequencing were performed at Biomarker Company (Beijing, China; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.biomarker.com.cn\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eThe raw data were processed through in-house perl scripts and the clean data Q20, Q30, and GC content were calculated. The clean data using for RNA de novo assembly by Trinity\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e which setting like min_kmer_cov as 2 and all others by default. Assembled transcript functions were annotated based on the NCBI non-redundant protein sequences (Nr), Protein family (Pfam), Swiss-Prot, Gene Ontology (GO), Clusters of Orthologous Groups of proteins (KOG/COG/eggNOG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases using BLASTX to identify the proteins.\u003c/p\u003e\n\u003cp\u003eThe DESeq R package (1.10.1) was used to provide statistical routines for determining differential expression. Genes with adjusting by the Benjamini and Hochberg approach, which P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were assigned as differentially expressed. The KOBAS software was used to test the statistical enrichment of differential expression genes in KEGG pathways\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e55\u003c/span\u003e\u003c/sup\u003e. The Gene Set Enrichment Analysis (GSEA) was using to show the variability of DESeq clursters within KEGG pathway\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e56\u003c/span\u003e\u003c/sup\u003e between the combination as NB3 vs CK3, NB3 vs Ld3, NB3 vs Ld6, CK3 vs Ld3, CK3 vs Ld6, Ld3 vs Ld6. The results of GESA were visualized with Cytoscape.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003cp\u003e\u003cstrong\u003eMetabolite extraction and analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEach group has six biological replicates, and the samples were prepared with following steps. 400 \u0026micro;L of iced Methanol/Acetonitrile (1: 1, v: v)(rank of LC-MS, CNW Technologies) was added into 100\u0026micro;L sample in 4\u0026deg;C and vortexed for 30sec, at \u0026minus;\u0026thinsp;20\u0026deg;C incubated for 20min, centrifuged at 14,000 rpm for 15 min at 4\u0026deg;C. Supernatant was transferred to a new tube and dried in a vacuum concentrator than using 100 \u0026micro;L of Acetonitrile/Water (1: 1, v: v) (rank of LC-MS, CNW Technologies) to reconstitute. 60\u0026micro;L aliquot of the supernatant was used to analysis via UHPLC-QTOF-MS.\u003c/p\u003e\n\u003cp\u003eThe LC-MS/MS analyses were performed using 1290 UHPLC system (Agilent Technologies) with ACQUITY UPLC BEH amide column (1.7\u0026micro;m, 2.1 mm \u0026times; 100 mm, Waters) coupled to a Triple TOF 5600 (Q-TOF, AB Sciex) instrument\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e57\u003c/span\u003e\u003c/sup\u003e. Analyst TF 1.7 software (AB Sciex) which was used to control the AB5600 TripleTOF(AB Sciex) continuously evaluates the full scan-surveyed MS data. And the mobile phase consisted of A and B which was passed through the elution gradient as 0 min, 95%B; 0.5 min, 95%B; 7 min, 65%B; 8 min, 40%B; 9 min, 40%B; 9.1 min, 95%B; and 12 min, 95% B, which was delivered at 500\u0026micro;L/min, and the injection volume was 2\u0026micro;L. A was 25mM Ammonium acelate (rank of LC-MS, CNW Technologies) and 25mM Ammonium hydroxide (rank of LC-MS, CNW Technologies) in water (pH\u0026thinsp;=\u0026thinsp;9.75), and B was Acetonitrile (rank of LC-MS, CNW Technologies). The electrospray ionization (ESI) source conditions were as follows: ion source gas 1 as 60psi; ion source gas 2 as 60; curtain gas as 30; source temperature of 550\u0026deg;C; and ion spray voltage floating (ISVF) at 5000 V or -4000 V in positive or negative mode, respectively.\u003c/p\u003e\n\u003cp\u003eBy using the SIMCA14 software package (Umetrics, Umea, Sweden), PCA (principal component analysis) and OPLS-DA (orthogonal projections to latent structures\u0026ndash;discriminate analysis) were implemented by with the results including peak numbers, sample names, and normalized peak areas. OPLS-DA was used to identify significantly different metabolites between the two comparison groups. The VIP values (variable importance for the projection values) were obtained to clarify the analysis, which exceeding 1.0 was first selected as different metabolites. Student\u0026rsquo;s T test was used to evaluate the remaining variables. The variables between groups were discarded with P\u0026thinsp;\u0026gt;\u0026thinsp;0.05. And each metabolite\u0026rsquo;s FC value (fold change value) was calculated by comparing the mean value of the peak area. The KEGG Online databases were used to search relate pathways, and differential metabolites were cross-linked to KEGG pathways.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntegrative analysis of metabolome and transcriptome\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003cp\u003eThe PCC (Pearson correlation coefficients) and CCA (canonical correlation analysis) were used to assess the integration of the metabolome and transcriptome. Transcriptome and metabolome datasets were combined to create a general metabolite-transcript network centred on genes according to the KEGG identification. The results of KEGG identification were visualized with Cytoscape.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Professor Liang-jian Qu from Chinese Academy of Forestry, Beijing, China for generously providing gypsy moth eggs. This study was supported by NSFC (No. 31670659).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRobert, Poulin., Fanny Maure.. 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The KEGG resource for deciphering the genome. \u003cem\u003eNucleic Acids Research\u003c/em\u003e, 32, D277-80. doi:10.1093/nar/gkh063 (2004)\u003c/li\u003e\n\u003cli\u003eSubramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L.. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. \u003cem\u003eProceedings of the National Academy of Sciences,\u003c/em\u003e 102(43), 15545-50. doi:10.1073/pnas.0506580102 (2005)\u003c/li\u003e\n\u003cli\u003eIvanisevic, J., Elias, D., Deguchi, H., Averell, P.M., Kurczy, M.. Arteriovenous Blood Metabolomics: A Readout of Intra-Tissue Metabostasis. \u003cem\u003eScientific Reports,\u003c/em\u003e 5, 12757. doi:10.1038/srep12757 (2015)\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eTable. 1 Amount of Annotated Metabolins in KEGG Databases of Positive Mode and Negative Mode\u003c/span\u003e\u003c/p\u003e\n\u003cdiv align=\"center\" style='margin:0in;text-align:justify;font-size:16px;font-family:\"Cambria\",serif;'\u003e\n \u003ctable style=\"border: none;width:564.85pt;border-collapse:collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.35pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:center;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eGroup\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family: \"Calibri\",sans-serif;'\u003eDifferent Number (POS)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eUp-regulated Number (POS)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.9pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eDown-regulated Number (POS) \u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eDifferent KEGG\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:13px;font-family: \"Calibri\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eNumber (POS)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eDifferent Number (NEG)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.9pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eUp-regulated Number(NEG)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eDown-regulated Number(NEG)\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eDifferent KEGG Number (NEG) \u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.35pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:center;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eNB3 vs CK\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e538\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.95pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e274\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e264\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e51\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e515\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e191\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.95pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e324\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e37\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.35pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:center;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eNB3 vs Ld3\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e871\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.95pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e374\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.9pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e495\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e81\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n 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style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e544\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e73\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.35pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:center;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eNB3 vs Ld6\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e865\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.95pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e431\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.9pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e434\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e71\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e870\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.9pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e288\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.95pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e582\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e73\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.35pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:center;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eLd3 vs Ld6\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e494\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.95pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e291\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.9pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e203\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e44\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e562\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.9pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e236\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.95pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e326\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e44\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.35pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:center;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eCK3 vs Ld3\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e605\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.95pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e258\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e347\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e71\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e752\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e336\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.95pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e416\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:61.95pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;margin-top:12.0pt;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e71\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;margin-top:12.0pt;text-indent:20.0pt;line-height:150%;'\u003e\u003cspan style='font-size:13px;line-height:150%;font-family:\"Calibri\",sans-serif;'\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003e\u003cbr\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;'\u003eTable. 2 KEGG Enrichment Pathways between Two Groups by Integrative Analysis of Metabolome and Transcriptome\u003c/span\u003e\u003c/p\u003e\n\u003cdiv align=\"center\" style='margin:0in;text-align:justify;font-size:16px;font-family:\"Cambria\",serif;'\u003e\n \u003ctable style=\"width: 5.6e+2pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:153.75pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eName of KEGG Pathway\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width:205.55pt;border:none;border-top: solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ePositive Mode\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width:205.55pt;border:none;border-top: solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eNegative Mode\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:41.1pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eNB3vsCK3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eNB3vsLd3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eNB3vsLd6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eLd3vsLd6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eCK3vsLd3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eNB3vsCK3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eNB3vsLd3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eNB3vsLd6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eLd3vsLd6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eCK3vsLd3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eCitrate cycle (TCA cycle)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e7\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ePentose phosphate pathway\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e7\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ePentose and glucuronate interconversions\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e24\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eFructose and mannose metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eGalactose metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e17\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e17\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e17\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e15\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eAscorbate and aldarate metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e17\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e19\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eFatty acid biosynthesis\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e15\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eFatty acid elongation\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eFatty acid degradation\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eSteroid biosynthesis\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eUbiquinone and other terpenoid-quinone biosynthesis\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eOxidative phosphorylation\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eArginine biosynthesis\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ePurine metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e35\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e7\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e28\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e31\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eCaffeine metabolism\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ePyrimidine metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e15\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e15\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e7\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eAlanine, aspartate and glutamate metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e19\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eGlycine, serine and threonine metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eCysteine and methionine metabolism\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eValine, leucine and isoleucine degradation\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eValine, leucine and isoleucine biosynthesis\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eLysine degradation\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eArginine and proline metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e7\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e15\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eHistidine metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eTyrosine metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e7\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ePhenylalanine metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e7\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eTryptophan metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ePhenylalanine, \u0026nbsp; \u0026nbsp; tyrosine and tryptophan biosynthesis\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ebeta-Alanine metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eTaurine and hypotaurine metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eD-Glutamine and D-glutamate metabolism\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eGlutathione metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e22\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e23\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eStarch and sucrose metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e7\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e19\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e20\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eAmino sugar and nucleotide sugar metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e20\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eGlycerolipid metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eInositol phosphate metabolism\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eGlycerophospholipid metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e18\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e24\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e15\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e21\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eArachidonic acid metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ealpha-Linolenic acid metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ePyruvate metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e20\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eGlyoxylate and dicarboxylate metabolism\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ePropanoate metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eButanoate metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eOne carbon pool by folate\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eNicotinate and nicotinamide metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ePantothenate and CoA biosynthesis\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eFolate biosynthesis\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ePorphyrin and chlorophyll metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eNitrogen metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e7\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eAminoacyl-tRNA biosynthesis\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eBiosynthesis of unsaturated fatty acids\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eCarbon metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e20\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e27\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2-Oxocarboxylic acid metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e19\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eFatty acid metabolism\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eBiosynthesis of amino acids\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e18\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e25\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e30\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e26\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e15\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e25\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e36\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e27\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eABC transporters\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e7\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e18\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e15\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eFoxO signaling pathway\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003ePhosphatidylinositol signaling system\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eNeuroactive ligand-receptor interaction\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003emTOR signaling pathway\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153.75pt;border: none;padding: 0in 5.4pt;height: 15pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:justify;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003eProtein digestion and absorption\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003e8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:15.0pt;\"\u003e\n \u003cp style='margin-right:0in;margin-left:0in;font-size:16px;font-family:\"Cambria\",serif;margin:0in;text-align:right;'\u003e\u003cspan style='font-size:13px;font-family:\"Calibri\",sans-serif;color:black;'\u003enon\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n 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Top Disease, Lymantria dispar larvae, pathway changes","lastPublishedDoi":"10.21203/rs.3.rs-414994/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-414994/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe pioneer record described the phenomenon of nucleopolyhedroviruses (NPVs) manipulating host behavior was named as Tree Top Disease or \u0026ldquo;Wipfelkrankheit\u0026rdquo; by Hofmann in 1891. Following publics advised multipartite effect during infection progressing that NPVs adjusting manipulated mode to actualize crossing barriers, immune escape and hormone regulation. In this study, the molecular mechanism of \u003cem\u003eLymantria dispar\u003c/em\u003e Multiple embedded Nucleopolyhedrovirus(LdMNPV)-infected was investigated by a comparison of transcriptomic and metabolomic analysis at four selected time points of LdMNPV-infected and healthy \u003cem\u003eLymantria dispar\u003c/em\u003e (Ld) larvae. Among data collecting, the notably up-regulated and down-regulated genes and metabolomics were used for further analysis. Integrative analysis revealed the content changes of caffeine, glutamate and gamma-Aminobutyric acid involved in LdMNPV inducing behavior change, and the alteration of myo-inositol, phosphatidyl-1D-myo-inositol and relevant genes involved in larval extended instar duration and apoptosis avoiding.\u003c/p\u003e","manuscriptTitle":"Integrated Transcriptomic and Metabolomic Analysis of Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV) infected Lymantria dispar in Tree-top Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-04-20 18:17:57","doi":"10.21203/rs.3.rs-414994/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"907330f0-856e-46ba-9bc7-baf1529c826c","owner":[],"postedDate":"April 20th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":3780531,"name":"Entomology"},{"id":3780532,"name":"Virology"},{"id":3780533,"name":"General Microbiology"}],"tags":[],"updatedAt":"2021-05-20T04:44:13+00:00","versionOfRecord":[],"versionCreatedAt":"2021-04-20 18:17:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-414994","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-414994","identity":"rs-414994","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}