P450 Genes: Structure, Evolution, and Regulation

P450 Genes: Structure, Evolution, and Regulation PERSPECTIVES AND SUMMARY Cytochromes P450 are enzymes involved in the oxidative metabolism of steroids, fatty acids, prostaglandins, leukotrienes, biogenic amines, pher­ omones, and plant metabolites. These enzymes also metabolize innumerable drugs, chemical carcinogens, mutagens , and other environmental contami­ nants. The large degree of overlapping substrate specificities, classes of inducing agents , and drug-drug interactions have caused great difficulty in P450 studies at the level of catalytic activities and protein immunochemistry. P450 enzymes represent the classical "Phase I" metabolism in which the substrate is oxygenated. "Phase II" enzymes often use the oxygen as a site for further metabolism (e.g. glucuronidation, and sulfate , glutathione , or glycine conjugation) . Detoxification usually requires both Phase I and Phase II en­ zymes. P450 enzymes play a large role in chemical mutagenesis and carcinogene­ sis. The initiation of cancer by foreign chemicals usually requires at least three steps. 1. Most compounds are inert and require metabolism to the ultimate carcinogenic form. 2. Adducts between DNA and these reactive intermediates escape the usual DNA repair processes and cause nucleotide changes and DNA rearrangements . 3 . The result of the first two steps leads to oncogene activation. Without P450 gene expression and, http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annual Review of Biochemistry Annual Reviews

P450 Genes: Structure, Evolution, and Regulation

Annual Review of Biochemistry, Volume 56 (1) – Jul 1, 1987

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Publisher
Annual Reviews
Copyright
Copyright 1987 Annual Reviews. All rights reserved
Subject
Review Articles
ISSN
0066-4154
eISSN
1545-4509
D.O.I.
10.1146/annurev.bi.56.070187.004501
Publisher site
See Article on Publisher Site

Abstract

PERSPECTIVES AND SUMMARY Cytochromes P450 are enzymes involved in the oxidative metabolism of steroids, fatty acids, prostaglandins, leukotrienes, biogenic amines, pher­ omones, and plant metabolites. These enzymes also metabolize innumerable drugs, chemical carcinogens, mutagens , and other environmental contami­ nants. The large degree of overlapping substrate specificities, classes of inducing agents , and drug-drug interactions have caused great difficulty in P450 studies at the level of catalytic activities and protein immunochemistry. P450 enzymes represent the classical "Phase I" metabolism in which the substrate is oxygenated. "Phase II" enzymes often use the oxygen as a site for further metabolism (e.g. glucuronidation, and sulfate , glutathione , or glycine conjugation) . Detoxification usually requires both Phase I and Phase II en­ zymes. P450 enzymes play a large role in chemical mutagenesis and carcinogene­ sis. The initiation of cancer by foreign chemicals usually requires at least three steps. 1. Most compounds are inert and require metabolism to the ultimate carcinogenic form. 2. Adducts between DNA and these reactive intermediates escape the usual DNA repair processes and cause nucleotide changes and DNA rearrangements . 3 . The result of the first two steps leads to oncogene activation. Without P450 gene expression and,

Journal

Annual Review of BiochemistryAnnual Reviews

Published: Jul 1, 1987

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