Molecular docking of omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to HMGCoA reductase -- the rate limiting enzyme of cholesterol biosynthesis

Molecular docking of omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to HMGCoA reductase -- the rate limiting enzyme of cholesterol biosynthesis | 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 Molecular docking of omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to HMGCoA reductase -- the rate limiting enzyme of cholesterol biosynthesis Shahdat Hossain This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4671645/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 Numerous studies show that fish oil components, particularly omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA: C20:5, w-3) and docosahexaenoic acid (DHA: (C22:6, w-3), lower blood cholesterol levels and claim that these PUFAs do this by inhibiting the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR). Statins, a group of commonly prescribed drugs to treat hypercholesterolemia, are also inhibitors of HMGCoAR. Since the intake of EPA and DHA lowers blood cholesterol levels, we used bioinformatics to investigate whether EPA and DHA actually bind to the inhibitor (statin) binding site of the HMGCoAR and thus limit the rise of blood cholesterol. Docking studies with HMGCoAR (1hw9) revealed that both EPA and DHA themselves can bind to the inhibitor binding site with a greater affinity than that of the statin. Therefore, it is concluded that purified EPA and DHA and/or fish oil containing them reduces blood cholesterol levels, at least in part, by directly inhibiting HMGCoAR. Computational Biology EPA (C20:5 ω-3) DHA (C20:6 ω-3) HMGCoAR Docking Hypercholesterolemia Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4671645","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":321520918,"identity":"34620fba-543d-4ee3-90f2-8c6d69f0b41f","order_by":0,"name":"Shahdat Hossain","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyElEQVRIiWNgGAWjYDACCQY2Bh4GBjnGBgaGA0A+iCZKi4Ex6VoSYSoJa5Gf3fzswZuaP+nNM3IPHuZhsJHdcICAFoM7x8wN5xwzyG2ckZcA1JJmTFiLRIKZNA8bSEuOwcEZDIcTCWqRn5H+TZrnn0E6I0TLf8JaGG7kmEnzthkkgLQc+MBwgLAWgxs5ZZJz+4wNG3veALUYJBvPJMJh2yTefJOTN2zPMf6QUGEn20fQYTBg2AC2lFjlYOtIUTwKRsEoGAUjCwAAjm9FwMH5+GAAAAAASUVORK5CYII=","orcid":"","institution":"Dept. of Biochemistry \u0026 Molecular Biology, Jahangirnagar University","correspondingAuthor":true,"prefix":"","firstName":"Shahdat","middleName":"","lastName":"Hossain","suffix":""}],"badges":[],"createdAt":"2024-07-02 05:40:39","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-4671645/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4671645/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":59544828,"identity":"8792f21a-5576-4868-bc1d-0e965161c444","added_by":"auto","created_at":"2024-07-03 04:53:39","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":376755,"visible":true,"origin":"","legend":"","description":"","filename":"Preprintsubmitted.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4671645/v1_covered_485dec7c-21bd-4daf-a15b-fbd275fec8bc.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eMolecular docking of omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to HMGCoA reductase -- the rate limiting enzyme of cholesterol biosynthesis\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[{"identity":"1f6b335a-a61c-4a45-abaf-722599dbc2ea","identifier":"10.13039/501100018644","name":"Jahangirnagar University","awardNumber":"122024","order_by":0}],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Jahangirnagar University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"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},"keywords":"EPA (C20:5, ω-3), DHA (C20:6, ω-3), HMGCoAR, Docking, Hypercholesterolemia","lastPublishedDoi":"10.21203/rs.3.rs-4671645/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4671645/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eNumerous studies show that fish oil components, particularly omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA: C20:5, w-3) and docosahexaenoic acid (DHA: (C22:6, w-3), lower blood cholesterol levels and claim that these PUFAs do this by inhibiting the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR). 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