Acetylenic mechanism-based inhibitors of cholesterol side chain cleavage by cytochrome P-450scc.
The following acetylenic steroids appear to be the first reported mechanism-based inhibitors of cytochrome P-450scc: 20-(1-propynyl)-5-pregnen-3 beta, 20 alpha-diol, 20-(1-hexynyl)-5-pregnen-3 beta, 20 alpha-diol, and 20-(1,5-hexadiynyl)5-pregnen-3 beta, 20 alpha-diol. Oxygen and NADPH are required for enzymatic oxidation and all three steroids yield pregnenolone as a major product. Incubation of P-450scc with 20-(1,5-hexadiynyl)-5-pregnen-3 beta, 20 alpha-diol under turnover conditions completely inactivates the enzyme with a half-time of 11 min. The partition ratio for inactivation by the steroid was determined to be about 6 molecules of the steroid processed per molecule of P-450scc inactivated.
D000325:Adrenodoxin / Q000378:metabolism; D000480:Alkynes / Q000494:pharmacology*; D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D005287:Ferredoxin-NADP Reductase / Q000378:metabolism; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000480:Alkynes; D065607:Cytochrome P-450 Enzyme Inhibitors; D000325:Adrenodoxin; D011284:Pregnenolone; C038240:20-(1-hexynyl)-5-pregnen-3,20-diol; C038241:20-(1,5-hexadiynyl)-5-pregnen-3,20-diol; C038239:20-(1-propynyl)-5-pregnen-3,20-diol; D005287:Ferredoxin-NADP Reductase