Cytochrome P450 Enzymes and Drug Metabolism in Humans

Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis. In humans, almost 80% of oxidative metabolism and approximately 50% of the overall elimination of common clinical drugs can be attributed to...

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Veröffentlicht in:	International journal of molecular sciences Jg. 22; H. 23; S. 12808
Hauptverfasser:	Zhao, Mingzhe, Ma, Jingsong, Li, Mo, Zhang, Yingtian, Jiang, Bixuan, Zhao, Xianglong, Huai, Cong, Shen, Lu, Zhang, Na, He, Lin, Qin, Shengying
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Switzerland MDPI AG 26.11.2021 MDPI
Schlagworte:	Animals Cancer therapies Clinical outcomes Cytochrome Cytochrome P-450 Enzyme System - genetics Cytochrome P-450 Enzyme System - metabolism Drugs Enzymes Epigenetics Humans Inactivation, Metabolic Ligands Metabolic Clearance Rate Metabolism Metabolites Pharmaceutical Preparations - metabolism Pharmaceuticals Polymorphism, Genetic Review Xenobiotics - metabolism protein structure cytochrome P450 genetic polymorphisms drug metabolism
ISSN:	1422-0067, 1661-6596, 1422-0067
Online-Zugang:	Volltext
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Abstract	Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis. In humans, almost 80% of oxidative metabolism and approximately 50% of the overall elimination of common clinical drugs can be attributed to one or more of the various CYPs, from the CYP families 1–3. In addition to the basic metabolic effects for elimination, CYPs are also capable of affecting drug responses by influencing drug action, safety, bioavailability, and drug resistance through metabolism, in both metabolic organs and local sites of action. Structures of CYPs have recently provided new insights into both understanding the mechanisms of drug metabolism and exploiting CYPs as drug targets. Genetic polymorphisms and epigenetic changes in CYP genes and environmental factors may be responsible for interethnic and interindividual variations in the therapeutic efficacy of drugs. In this review, we summarize and highlight the structural knowledge about CYPs and the major CYPs in drug metabolism. Additionally, genetic and epigenetic factors, as well as several intrinsic and extrinsic factors that contribute to interindividual variation in drug response are also reviewed, to reveal the multifarious and important roles of CYP-mediated metabolism and elimination in drug therapy.
AbstractList	Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis. In humans, almost 80% of oxidative metabolism and approximately 50% of the overall elimination of common clinical drugs can be attributed to one or more of the various CYPs, from the CYP families 1–3. In addition to the basic metabolic effects for elimination, CYPs are also capable of affecting drug responses by influencing drug action, safety, bioavailability, and drug resistance through metabolism, in both metabolic organs and local sites of action. Structures of CYPs have recently provided new insights into both understanding the mechanisms of drug metabolism and exploiting CYPs as drug targets. Genetic polymorphisms and epigenetic changes in CYP genes and environmental factors may be responsible for interethnic and interindividual variations in the therapeutic efficacy of drugs. In this review, we summarize and highlight the structural knowledge about CYPs and the major CYPs in drug metabolism. Additionally, genetic and epigenetic factors, as well as several intrinsic and extrinsic factors that contribute to interindividual variation in drug response are also reviewed, to reveal the multifarious and important roles of CYP-mediated metabolism and elimination in drug therapy. Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis. In humans, almost 80% of oxidative metabolism and approximately 50% of the overall elimination of common clinical drugs can be attributed to one or more of the various CYPs, from the CYP families 1-3. In addition to the basic metabolic effects for elimination, CYPs are also capable of affecting drug responses by influencing drug action, safety, bioavailability, and drug resistance through metabolism, in both metabolic organs and local sites of action. Structures of CYPs have recently provided new insights into both understanding the mechanisms of drug metabolism and exploiting CYPs as drug targets. Genetic polymorphisms and epigenetic changes in CYP genes and environmental factors may be responsible for interethnic and interindividual variations in the therapeutic efficacy of drugs. In this review, we summarize and highlight the structural knowledge about CYPs and the major CYPs in drug metabolism. Additionally, genetic and epigenetic factors, as well as several intrinsic and extrinsic factors that contribute to interindividual variation in drug response are also reviewed, to reveal the multifarious and important roles of CYP-mediated metabolism and elimination in drug therapy.Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis. In humans, almost 80% of oxidative metabolism and approximately 50% of the overall elimination of common clinical drugs can be attributed to one or more of the various CYPs, from the CYP families 1-3. In addition to the basic metabolic effects for elimination, CYPs are also capable of affecting drug responses by influencing drug action, safety, bioavailability, and drug resistance through metabolism, in both metabolic organs and local sites of action. Structures of CYPs have recently provided new insights into both understanding the mechanisms of drug metabolism and exploiting CYPs as drug targets. Genetic polymorphisms and epigenetic changes in CYP genes and environmental factors may be responsible for interethnic and interindividual variations in the therapeutic efficacy of drugs. In this review, we summarize and highlight the structural knowledge about CYPs and the major CYPs in drug metabolism. Additionally, genetic and epigenetic factors, as well as several intrinsic and extrinsic factors that contribute to interindividual variation in drug response are also reviewed, to reveal the multifarious and important roles of CYP-mediated metabolism and elimination in drug therapy.
Author	Zhao, Xianglong He, Lin Jiang, Bixuan Huai, Cong Zhang, Na Ma, Jingsong Zhao, Mingzhe Zhang, Yingtian Qin, Shengying Shen, Lu Li, Mo
AuthorAffiliation	1 Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China; zhaomingzhe@sjtu.edu.cn (M.Z.); limo1169718691@sjtu.edu.cn (M.L.); zhangyingtian@sjtu.edu.cn (Y.Z.); bixuanjiang@sjtu.edu.cn (B.J.); zhaoxianglong2011@sjtu.edu.cn (X.Z.); huaic@sjtu.edu.cn (C.H.); mailer.shen@gmail.com (L.S.); zhangnazn@sjtu.edu.cn (N.Z.); helin@sjtu.edu.cn (L.H.) 2 Institutes for Shanghai Pudong Decoding Life, Shanghai 200135, China; majingsong@westlake.edu.cn
AuthorAffiliation_xml	– name: 1 Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China; zhaomingzhe@sjtu.edu.cn (M.Z.); limo1169718691@sjtu.edu.cn (M.L.); zhangyingtian@sjtu.edu.cn (Y.Z.); bixuanjiang@sjtu.edu.cn (B.J.); zhaoxianglong2011@sjtu.edu.cn (X.Z.); huaic@sjtu.edu.cn (C.H.); mailer.shen@gmail.com (L.S.); zhangnazn@sjtu.edu.cn (N.Z.); helin@sjtu.edu.cn (L.H.) – name: 2 Institutes for Shanghai Pudong Decoding Life, Shanghai 200135, China; majingsong@westlake.edu.cn
Author_xml	– sequence: 1 givenname: Mingzhe surname: Zhao fullname: Zhao, Mingzhe – sequence: 2 givenname: Jingsong surname: Ma fullname: Ma, Jingsong – sequence: 3 givenname: Mo orcidid: 0000-0002-9915-1348 surname: Li fullname: Li, Mo – sequence: 4 givenname: Yingtian surname: Zhang fullname: Zhang, Yingtian – sequence: 5 givenname: Bixuan surname: Jiang fullname: Jiang, Bixuan – sequence: 6 givenname: Xianglong surname: Zhao fullname: Zhao, Xianglong – sequence: 7 givenname: Cong surname: Huai fullname: Huai, Cong – sequence: 8 givenname: Lu surname: Shen fullname: Shen, Lu – sequence: 9 givenname: Na surname: Zhang fullname: Zhang, Na – sequence: 10 givenname: Lin surname: He fullname: He, Lin – sequence: 11 givenname: Shengying orcidid: 0000-0002-8458-5960 surname: Qin fullname: Qin, Shengying
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/34884615$$D View this record in MEDLINE/PubMed
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Issue	23
Keywords	protein structure cytochrome P450 genetic polymorphisms drug metabolism
Language	English
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Snippet	Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis....
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SubjectTerms	Animals Cancer therapies Clinical outcomes Cytochrome Cytochrome P-450 Enzyme System - genetics Cytochrome P-450 Enzyme System - metabolism Drugs Enzymes Epigenetics Humans Inactivation, Metabolic Ligands Metabolic Clearance Rate Metabolism Metabolites Pharmaceutical Preparations - metabolism Pharmaceuticals Polymorphism, Genetic Review Xenobiotics - metabolism
Title	Cytochrome P450 Enzymes and Drug Metabolism in Humans
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