Summary
Human cytochrome P450 enzymes involved in the metabolism of exogenous and endogenous compounds are intensively studied. The regulation of cytochromes P450 by transcriptional activation via the Ah receptor (CYP1A) and peroxisome proliferator activated receptor (CYP4A) is increasingly understood at the molecular level, in contrast to induction by phénobarbital and glucocorticoids. The tissue-specific and developmental regulation of P450s by transcription factors such as HNF-Iα, DBP, C/EBP and Spl is complex. Individual variation of the activity of these enzymes is markedly influenced by common genetic polymorphisms, with numerous loss of function or decreased function and even increased function alleles of P450 genes. There is evidence for an important role of P450 enzymes in the activation of carcinogens. Variable extrahepatic expression of human P450s may contribute to individual cancer risk. Progress has also been made in the understanding of the role of P4507α (cholesterol 7α hydroxylase) in cholesterol homeostasis.
Human cytochrome P450 (P450) enzymes are the subject of intensive research because of their obvious relevance to drug therapy and toxicity and their role in chemical carcinogenesis. Moreover, the biotransformation of numerous endogenous compounds such as steroids, retinoids, eicosanoids, and other endogenous compounds is catalyzed by P450s. The super-family of P450 genes comprises over 300 genes in various species. Of these, over 40 human P450 enzymes are known and classified within the 13 mammalian gene families.
From the Symposium “Human Cytochromes P450: Regulation and Functional Variability”
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© 1995 Birkhäuser Verlag Basel/Switzerland
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Meyer, U.A., Gonzalez, F.J., Peter Guengerich, F., McManus, M.E., Okuda, KI. (1995). Human Cytochromes P450: Regulation and Functional Variability. In: Cuello, A.C., Collier, B. (eds) Pharmacological Sciences: Perspectives for Research and Therapy in the Late 1990s. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7218-8_15
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