Philosophical Transactions of the Royal Society B: Biological Sciences
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Human cytochromes P450 in health and disease

Daniel W. Nebert

Daniel W. Nebert

Department of Environmental Health, Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, OH 45267-0056, USA

[email protected]

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,
Kjell Wikvall

Kjell Wikvall

Department of Pharmaceutical Biosciences, Division of Biochemistry, University of Uppsala, Uppsala 751 23, Sweden

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and
Walter L. Miller

Walter L. Miller

Department of Pediatrics, Division of Endocrinology, University of California, San Francisco, CA 94143-1346, USA

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Published:https://doi.org/10.1098/rstb.2012.0431

    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.

    Footnotes

    One contribution of 9 to a Theme Issue ‘Cytochrome P450 and its impact on planet Earth’.

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