CYTOCHROME P-450(SCC)-CATALYZED PRODUCTION OF PROGESTERONE FROM CHOLESTENONE

Cholestenone, which is a 3-keto derivative of cholesterol, was incubat ed with cytochrome P-450(scc) in a reconstituted hydroxylation system. Cholestenone was metabolized to progesterone with a turnover number o f about 9 nmol/min/nmol P-450 in the presence of 0.01% Tween20. This v alue was about 70% of the maximal value for cholesterol. The final rea ction product, progesterone, and three other minor reaction products, 20 alpha-hydroxycholest-4-en-3-one, 22R-hydroxycholest-4-en-3-one, 20, 22-dihydroxycholest-4-en-3-one, were identified on the basis of its re tention times on HPLC, thus suggesting them to be intermediates of sid e-chain cleavage of cholestenone. The results suggest that cholestenon e is metabolized by two pathways, that is, the first hydroxylation occ urs either at the C-20 position or at the C-22 position.