Competitive inhibition of cytochrome P-450scc by (22R)- and (22S)-22-aminocholesterol. Side-chain stereochemical requirements for C-22 amine coordination to the active-site heme.
Two diastereomeric aminocholesterols, (22R)-22-aminocholesterol and (22S)-22-aminocholesterol, are both found to be potent inhibitors of the biosynthesis of pregnenolone from cholesterol by purified bovine mitochondrial P-450scc. Both steroids are competitive versus cholesterol, but the stereochemically correct analog (22R)-22-aminocholesterol is bound approximately 1000 times more tightly than (22S)-22-aminocholesterol. The dissociation constants are 25 nM and 13 microM, respectively. Direct comparisons between spectroscopic and enzymatic properties of the two enzymesterol complexes and the 22-amino-23,24-bisnor-5-cholen-3 beta-ol complex are made, underlining the importance of the stereochemistry at the C-22 position.
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D006418:Heme / Q000378:metabolism; D007700:Kinetics; D013053:Spectrophotometry; D013237:Stereoisomerism
D065607:Cytochrome P-450 Enzyme Inhibitors; D006418:Heme; C006517:22-aminocholesterol; D002784:Cholesterol