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Molecular Pharmacology, Vol 5, 123-130, Copyright © 1969 by the American Society for Pharmacology and Experimental Therapeutics

Studies on the Relationship between the Effects of Various Substances on Absorption Spectrum of Cytochrome P-450 and the Reduction of p-Nitrobenzoate by Mouse Liver Microsomes

HENRY A. SASAME 1 and JAMES R. GILLETTE 1

1 Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, Maryland 20014

The reduction of p-nitrobenzoate by an NADPH-dependent enzyme in liver microsomes is presumably mediated by cytochrome P-450. The reaction is inhibited by substances which cause type II spectral changes in liver microsomes, but not by those which cause type I spectral changes. Type II substances inhibit only about 50% of the nitroreductase activity in liver microsomes. The apparent Ki values for the inhibition of p-nitrobenzoate reduction are approximately double the K[unknown], values of the various type II substances studied. The evidence suggests that type II substances inhibit p-nitrobenzoate reduction by slowing the rate of cytochrome P-450 reduction.

Submitted on September 30, 1968




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