Abstract
In rat liver microsomes, 2-methyl-1,4-naphthoquinone (menadione) inhibits cytochrome P450 (cyt P450)-mediated aniline-p-hydroxylation and aminopyrine-N-demethylation with K i values of 12 and 14.5 μ m, respectively. The inhibitions of aniline-p-hydroxylation and aminopyrine-N-demethylation are mixed uncompetitive-noncompetitive and mixed competitive-noncompetitive, respectively. NADP antagonizes the inhibitory effect of menadione on aniline- p-hydroxylase activity but not that on aminopyrine- N-demethylase activity. Menadione does not give rise to any spectral change of cyt P450, but modifies the type I binding spectrum induced by aminopyrine. In contrast, menadione does not change the type II binding spectrum induced by aniline. These results indicate that menadione may inhibit aniline- p-hydroxylase activity by acting as a substrate for NADPH-cyt P450 reductase in the place of cyt P450 and inhibit aminopyrine- N-demethylase activity by impairing the binding of aminopyrine to cyt P450.
Published Version
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