Reconstituted liver microsomal enzyme system that hydroxylates drugs, other foreign compounds and endogenous substrates: V. Competition between cytochromes P-450 and P-448 for reductase in 3,4-benzpyrene hydroxylation

Abstract

The competition between cytochromes P-450 (from rats treated with phenobarbital) and P-448 (from rats treated with 3-methylcholanthrene) for reductase in the 3,4-benzpyrene hydroxylation reaction was studied using the reconstituted microsomal hydroxylation system. Cytochrome P-450 stimulated the rate of reaction at low concentrations of cytochrome P-448 but inhibited the reaction at higher concentrations of cytochrome P-448. The inhibition of cytochrome P-448-supported 3,4-benzpyrene hydroxylation by cytochrome P-450 could be reversed by increasing the concentration of reductase. The kinetic data were consistent with the view that cytochromes P-450 and P-448 compete for the reductase in the reaction mixture.