Inhibition of bovine adrenocortical cytochrome P-450scc by 3,3'-dimethoxybenzidine.
The effect of 3,3'=dimethoxybenzidine (o-dianisidine) on the conversion of cholesterol to pregnenolone was investigated in a reconstituted side chain cleavage system using enzymes purified from bovine adrenal cortex; d-p-aminoglutethimide was also assayed under similar conditions for comparison. 3,3'-Dimethoxybenzidine was found to be a potent inhibitor of pregnenolone formation, causing 50% inhibition at a concentration of 1.5 microM when using 70 microM cholesterol - this dose is approximately one fourth that required of 3-methoxybenzidine and one twentieth that required of benzidine for equal inhibition. In the same system, d-p-aminoglutethimide exhibited an I50 value of about 55 microM. No effects of 3,3'-dimethoxybenzidine on adrenodoxin reductase or adrenodoxin activities could be detected, and inhibition of side chain cleavage could be relieved by dilution suggesting that the inhibitor acts by reversibly binding to cytochrome P-450scc.
D000302:Adrenal Cortex / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D001560:Benzidines / Q000494:pharmacology*; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003962:Dianisidine / Q000494:pharmacology*; D007700:Kinetics; D011284:Pregnenolone / Q000096:biosynthesis
D001560:Benzidines; D065607:Cytochrome P-450 Enzyme Inhibitors; D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D003962:Dianisidine