Abstract
Ethylmorphine N-demethylase, aniline hydroxylase, and 3,4-benzo[a]pyrene hydroxylase of hepatic microsomes were inhibited 22-32% by substitution of D2O for H2O in the incubation medium. The effect on the first two enzymes was not related to the pH or the time course of incubation. The inhibition was linear with D2O concentration, occurred immediately, and was rapidly reversible. The inhibition was purely noncompetitive. NADPH-cytochrome c reductase in the intact microsomes was inhibited 15%, while in the solubilized form it was inhibited 51%. Basal NADPH oxidase and NADP—cytochrome P-450 reductase activities were not greatly affected, but were significantly inhibited in the presence of 2 mM ethylmorphine. In both cases the difference between the stimulated and basal activities was stoichiometric with ethylmorphine N-demethylase and exhibited the same degree of inhibition. These findings suggest that, in spite of the lipid nature of the microsomal membrane, changes in hydration of the lipoprotein play a significant role in the mixed-function oxidases.
- Copyright ©, 1972, by Academic Press, Inc.
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