3-Methoxybenzidine: a potent inhibitor of cholesterol side chain cleavage cytochrome P-450.
The effect of 3-methoxybenzidine on the conversion of cholesterol to pregnenolone was investigated using a reconstituted enzyme system comprised of adrenodoxin, adrenodoxin reductase and cytochrome P-450scc purified from bovine adrenal cortex. Under conditions where the cytochrome P-450scc concentration was rate-limiting, 3-methoxybenzidine was found to be a potent inhibitor, causing 50% inhibition at 7 microM when using a cholesterol concentration of 70 microM. The parent compound, benzidine, was much less effective, exhibiting an I50 value of approximately 40 microM. No effect of 3-methoxybenzidine was observed on the adrenodoxin reductase and adrenodoxin-catalyzed reduction of cytochrome c by NADPH, and it is concluded that 3-methoxybenzidine acts on cytochrome P-450scc in inhibiting cholesterol side chain cleavage.
D000302:Adrenal Cortex / Q000378:metabolism; D000325:Adrenodoxin / Q000378:metabolism; D000818:Animals; D001560:Benzidines / Q000494:pharmacology*; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D005287:Ferredoxin-NADP Reductase / Q000378:metabolism; D066298:In Vitro Techniques; D011284:Pregnenolone / Q000096:biosynthesis*
D001560:Benzidines; D065607:Cytochrome P-450 Enzyme Inhibitors; D000325:Adrenodoxin; C027665:3-methoxybenzidine; D011284:Pregnenolone; D002784:Cholesterol; D005287:Ferredoxin-NADP Reductase