Title: | Human cytochromes P450 in health and disease |
Author(s): | Nebert DW; Wikvall K; Miller WL; |
Address: | "Department of Environmental Health, Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, OH 45267-0056, USA. dan.nebert@uc.edu" |
Journal Title: | Philos Trans R Soc Lond B Biol Sci |
ISSN/ISBN: | 1471-2970 (Electronic) 0962-8436 (Print) 0962-8436 (Linking) |
Abstract: | "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" |
Keywords: | "Animals Cholesterol/biosynthesis/metabolism Cytochrome P-450 Enzyme System/classification/genetics/*metabolism Dehydroepiandrosterone/metabolism Eicosanoids/metabolism Enzyme Activation Evolution, Molecular Humans Hydroxylation Metabolic Diseases/*enzymol;" |
Notes: | "MedlineNebert, Daniel W Wikvall, Kjell Miller, Walter L eng P30 ES006096/ES/NIEHS NIH HHS/ R01 DK037922/DK/NIDDK NIH HHS/ R01 GM037020/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review England 2013/01/09 Philos Trans R Soc Lond B Biol Sci. 2013 Jan 6; 368(1612):20120431. doi: 10.1098/rstb.2012.0431. Print 2013 Feb 19" |