Cited by 1,070Pharmacogenetics and Drug MetabolismDrug Transport and Resistance MechanismsMetal-Catalyzed Oxygenation Mechanisms

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Cytochrome P450 Enzymes and Drug Metabolism in Humans

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Zhao, Mingzhe, Ma, Jingsong, Li, Mo, Zhang, Yingtian, Jiang, Bixuan, Zhao, Xianglong, Huai, Cong, Shen, Lu, Zhang, Na, He, Lin, Qin, Shengying·2021·International Journal of Molecular Sciences

DOI 10.3390/ijms222312808PMC PMC8657965

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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.

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Authors: Zhao, M., Ma, J., Li, M., Zhang, Y., Jiang, B., Zhao, X., Huai, C., Shen, L., Zhang, N., He, L., & Qin, S.
Affiliations: Shanghai Jiao Tong University (CN)
Institutes for Shanghai Pudong Decoding Life, Shanghai 200135, China
Corresponding author: Qin, Shengying
ORCID: Zhao, Mingzhe
Li, Mo
Zhang, Yingtian
Zhao, Xianglong
Huai, Cong
Shen, Lu
Zhang, Na
He, Lin
Qin, Shengying
Venue: International Journal of Molecular Sciences
Publisher: MDPI AG
Published: 2021-11-26
Volume: 22
Issue: 23
Pages: 12808
ISSN: 1422-0067 (ISSN-L)
DOI: 10.3390/ijms222312808
PMC: PMC8657965
OpenAlex: W3216238012
Cited by: 1,070
References: 124
Citations by year: 2026: 255 · 2025: 349 · 2024: 301 · 2023: 134 · 2022: 30
FWCI: 20.56
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: International Journal of Molecular Sciences (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Nature Science Foundation of China (81773818, 81273596, 30900799, 81671326)
National key research and development program (2016YFC0905000, 2016YFC0905002, 2016YFC1200200, 2016YFC0906400)
111 project, Shanghai Pujiang Program (17PJD020)
Shanghai Key Laboratory of Psychotic Disorders (13dz2260500)
Shanghai Science and Technology Innovation Fund (20DZ2202000, 21002411100)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
Keywords: cytochrome P450, drug metabolism, human drug metabolism, CYP1A2, CYP2C9, CYP2C19, CYP3A4, CYP2D6, CYP2B6, CYP2A6, CYP2E1, CYP1B1, CYP1A1
MeSH terms: Animals, Cytochrome P-450 Enzyme System, Pharmaceutical Preparations, Humans, Metabolic Clearance Rate, Inactivation, Metabolic, Polymorphism, Genetic, Xenobiotics

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Cytochrome P450 Enzymes and Drug Metabolism in Humans

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