PERSPECTIVES AND SUMMARY Cytochromes P450 are enzymes involved in the oxidative metabolism of steroids, fatty acids, prostaglandins, leukotrienes, biogenic amines, pherÂ omones, and plant metabolites. These enzymes also metabolize innumerable drugs, chemical carcinogens, mutagens , and other environmental contamiÂ 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 enÂ zymes. P450 enzymes play a large role in chemical mutagenesis and carcinogeneÂ 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,
Annual Review of Biochemistry – Annual Reviews
Published: Jul 1, 1987
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