Human cytochromes P450 in health and disease
Open accessAbstract
There are 18 mammalian cytochrome P450 ( CYP ) families, which encode 57 genes in the human genome. CYP2 , CYP3 and CYP4 families contain far more genes than the other 15 families; these three families are also the ones that are dramatically larger in rodent genomes. Most (if not all) genes in the CYP1 , CYP2 , CYP3 and CYP4 families encode enzymes involved in eicosanoid metabolism and are inducible by various environmental stimuli (i.e. diet, chemical inducers, drugs, pheromones, etc.), whereas the other 14 gene families often have only a single member, and are rarely if ever inducible or redundant. Although the CYP2 and CYP3 families can be regarded as largely redundant and promiscuous, mutations or other defects in one or more genes of the remaining 16 gene families are primarily the ones responsible for P450-specific diseases—confirming these genes are not superfluous or promiscuous but rather are more directly involved in critical life functions. P450-mediated diseases comprise those caused by: aberrant steroidogenesis; defects in fatty acid, cholesterol and bile acid pathways; vitamin D dysregulation and retinoid (as well as putative eicosanoid) dysregulation during fertilization, implantation, embryogenesis, foetogenesis and neonatal development.
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Mitochondrial CYPs utilize an electron transport chain containing ferredoxin reductase (FDXR) and ferredoxin proteins.
“While ER-localized CYPs obtain their electrons from a single P450 oxidoreductase, the mitochondrial CYPs utilize an electron transport chain containing the ferredoxin reductase (FDXR) and ferredoxin proteins (34).”
From Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies (2016) · cites this paper as [34]
Microsomal P450 enzymes require P450 oxidoreductase (POR) for electron transfer.
“In the endoplasmic reticulum ('microsomes') NADPH donates electrons to the 82-kDa, 2-flavin protein POR, which then donates them to the microsomal steroidogenic P450 enzymes”
From Steroidogenic electron-transfer factors and their diseases (2021) · cites this paper as [16]
The human genome encodes 57 cytochrome P450 enzymes, of which 7 are type 1 and 50 are type 2.
“There are 2 types of human P450 enzymes, type 1 in the mitochondria and type 2 in the endoplasmic reticulum; the human genome encodes 57 cytochrome P450 enzymes, of which 7 are type 1 and 50 are type 2”
From Steroidogenic electron-transfer factors and their diseases (2021) · cites this paper as [16]
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Disorders in the initial steps of steroid hormone synthesis
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BackgroundSteroidogenic electron-transfer factors and their diseases
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Self-citation
- Authors
- Nebert, D. W., Wikvall, K., & Miller, W. L.
- Affiliations
- University of Cincinnati Medical Center (US)
- Uppsala University (SE)
- University of California, San Francisco (US)
- Corresponding author
- Nebert, Daniel W.
- ORCID
- Miller, Walter L.
- Venue
- Philosophical Transactions of the Royal Society B: Biological Sciences
- Publisher
- The Royal Society
- Published
- 2013-02-19
- Volume
- 368
- Issue
- 1612
- Pages
- 20120431
- ISSN
- 0962-8436 (ISSN-L)
- 1471-2970
- PMC
- PMC3538421
- OpenAlex
- W2147971048
- Cited by
- 505
- References
- 177
- Citations by year
- 2026: 12 · 2025: 29 · 2024: 46 · 2023: 42 · 2022: 55 · 2021: 63 · 2020: 36 · 2019: 51 · 2018: 40 · 2017: 37 · 2016: 32 · 2015: 25 · 2014: 25 · 2013: 11
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Vetenskapsrådet
- National Institutes of Health (NIH-R01, ES006096)
- National Institute of General Medical Sciences (R01 GM037020)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK037922)
- National Institute of Environmental Health Sciences (P30ES006096)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Keywords
- cytochrome P450, eicosanoid metabolism, enzyme induction, steroidogenesis, fatty acid metabolism, bile acid metabolism, vitamin D, retinoids, genetic disorders, embryonic development, fertilisation (biology), implantation, neonatal development
- MeSH terms
- Animals, Cholesterol, Cytochrome P-450 Enzyme System, Dehydroepiandrosterone, Enzyme Activation, Multigene Family, Humans, Hydroxylation, Metabolic Diseases, Oxidation-Reduction, Pregnenolone, Tretinoin, Vitamin D, Eicosanoids, Evolution, Molecular
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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