Formation of Potentially Toxic Metabolites of Polycyclic Aromatic Compounds (PAHs) in Reactions Catalyzed by Human Metabolizing Enzymes

Data are presented on the formation of potentially toxic metabolites of polycyclic aromatic hydrocarbons (PAHs) and the effects of the structure of the compounds on the human metabolic enzymes that catalyze the reactions and the products formed. The tabular data lists the formation of potentially toxic/reactive products. The data obtained from in vitro experiments showed that the oxidative reactions predominate (67% of the potentially toxic reactions). Sulfating reactions participate in 14%, reductions with 12%, and acetylation reactions with 7%. Of the enzymes, cytochrome P450 (P450, CYP) enzymes catalyzed 58% of the reactions, aldo-keto reductases (AKR) 16%, sulfotransferases (SULT) 15%, N-acetyltransferases (NAT) 6%, cytochrome P450 reductase (NPR) 3%, and a group of minor participating enzymes to the extent of 3%. Within the P450 Superfamily, P450 Family 1 (P450 1A1, 1A2, 1B1) participates to the extent of 75%, P450 3A4 with 8%, P450 2W1 with 4%, and the group of minor participating enzymes with 13%. In the C- and N-atom(s)-containing PAHs (N-PAHs), the P450 enzymes dominated with 66%, followed by NAT (14%), SULT (11%), and the group of minor participating enzymes (9%). The P450 Family 1 dominated with 67%. In the C- atom-containing group of PAHs (C-PAHs), the P450 enzymes participated with 51%. AKR with 28%, SULT with 19%, and COX and EH enzymes with 2%. Of the P450 Family 1 enzymes, P450 1A1 dominated with 41% of the reactions. The data show the dominant participation of the P450 enzymes and the effect of the N-atom presence on the toxication reactions of PAHs and the metabolites formed. Selected examples of the PAHs that are activated or proposed to form toxic species are discussed.