Non-competitive and competitive inhibition of mixed function oxidase in rat liver microsomes by metyrapone.

Abstract

N-demethylation of aminopyrine and ethylmorphine via hepatic microsomal mixed function oxidase cytochrome P-450 from rat is inhibited by metyrapone by two mechanisms: Non-competitive inhibition occurs at low concentrations (Ki about 2·10−6 M); competitive inhibition is obtained at high concentrations (Ki about 1·10−4 M). Lineweaver-Burk kinetics allow to determine the Ki for inhibition at high concentrations. The Ki for inhibition with low concentrations has been obtained by extrapolation. The inhibitor concentrations which yield 50% inhibition have been plotted versus vmax at different protein dilutions.