The effect of steroid hydroxylase inhibitors on the rate of reduction of adrenal mitochondrial cytochrome P-450

Abstract

When added to adrenocortical mitochondria, metyrapone, amphenone and aminoglutethimide induce type II difference spectra, and block both the initial rate of malate-linked cytochrome P-450 reduction and also the DOC-induced increase in this rate. Removing the -NH2 group from aminoglutethimide shifts the spectrum to shorter wavelengths and reduces its effectiveness in blocking P-450 reduction. These compounds appear to block steroid hydroxylation by binding to oxidized P-450 and only very slowly allowing the P-450 to be reduced.