Reconstituted Liver Microsomal Enzyme System That Hydroxylates Drugs, Other Foreign Compounds, and Endogenous Substrates

作者：Anthony Y.H. Lu, Wayne Levin, SUSAN B. WEST, Martin Jacobson, Dene E. Ryan, Ronald G. Kuntzman, Allan H. Conney · 发表于：Journal of Biological Chemistry · 年份：1973 · DOI：10.1016/s0021-9258(19)44395-0 · 被引用次数：208 · 研究领域：Pharmacogenetics and Drug Metabolism、Hormonal and reproductive studies、Eicosanoids and Hypertension Pharmacology

Abstract The substrate specificities of the liver microsomal cytochrome P450 fractions from control and phenobarbital-treated immature, male rats were studied with the reconstituted hydroxylation system. In the presence of fixed amounts of the reductase and lipid fractions and various amounts of hemoprotein, the catalytic activities of the cytochrome P450 fractions from control and phenobarbital-treated rats were compared with a variety of substrates. Both fractions were about equally active for the N-demethylation of ethylmorphine and the hydroxylation of testosterone at positions 6β and 7α. However, the cytochrome P450 fraction from phenobarbital-treated rats was much more active than the cytochrome P450 fraction from control rats for the N-demethylation of benzphetamine and chlorcyclizine, the oxidation of pentobarbital, and the hydroxylation of testosterone at position 16α. For the hydroxylation of 3,4-benzpyrene, the cytochrome P450 fraction from control rats was slightly more active than the P450 fraction from phenobarbital-treated rats. These results suggest that the cytochrome P450 from control rats is catalytically different from the cytochrome P450 from phenobarbital-treated rats. The cytochrome P448 fraction from rats treated with 3-methylcholanthrene was also assayed for its ability to metabolize various substrates. The substrate specificity of the cytochrome P448 fraction differed from both cytochrome P450 fractions.