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

The DOI matches its Crossref record; 119 of the 124 references it cites were found in a registry or an index.

Cytochrome P450 Enzymes and Drug Metabolism in Humans

Open access
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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Crossref · 10.3390/ijms222312808

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Figure 1 General pathways of drug metabolism.
Figure 1 General pathways of drug metabolism.CC BY · PubMed Central
Figure 2 Contribution of different enzymes to drug metabolism. UGT, UDG glucuronosyl transferase; FMO, flavin-containing monooxygenase; NAT, N-acetyltransferase; MAO, monoamine oxidase.
Figure 2 Contribution of different enzymes to drug metabolism. UGT, UDG glucuronosyl transferase; FMO, flavin-containing monooxygenase; NAT, N-acetyltransferase; MAO, monoamine oxidase.CC BY · PubMed Central
Figure 3 A representative example of known CYP structures, illustrating the common three-dimensional fold.
Figure 3 A representative example of known CYP structures, illustrating the common three-dimensional fold.CC BY · PubMed Central
Figure 4 Fraction of specific CYP isoforms contribution to 248 drug metabolisms.
Figure 4 Fraction of specific CYP isoforms contribution to 248 drug metabolisms.CC BY · PubMed Central
Figure 5 Types of reversible inhibition.
Figure 5 Types of reversible inhibition.CC BY · PubMed Central

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Metadata

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
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
Licence
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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