15-Oxygenated sterols. Enzymatic conversion of [2,4]3H]5 alpha-cholest-8(14)-en-3 beta-ol-15-one to cholesterol in rat liver homogenate preparations.

5 alpha-Cholest-8(14)-en-3 beta-ol-15-one is a very potent inhibitor of sterol biosynthesis in animal cells in culture (G. J. Schroepfer, Jr., E. J. Parish, H. W. Chen, and A. A. Kandutsch (1977) J. Biol. Chem. 252, 8975-8980) and has significant hypocholesterolemic activity upon dietary administration to normal animals (G. J. Schroepfer, Jr., D. Monger, A. S. Taylor, J. S. Chamberlain, E. J. Parish, A. Kisic, and A. A. Kandutsch (1977) Biochem. Biophys. Res. Commun. 78, 1227-1233). In the present study we have prepared [2,4-3H]5 alpha-cholest-8(14)-en-3 beta-ol-15-one by chemical synthesis. This compound has been shown to be convertible to cholesterol upon incubation with the 10,000 X g supernatant fraction of rat liver homogenates under aerobic conditions. The efficiency of this conversion was higher in preparations derived from male rats than in those obtained from female rats. Labeled 5 alpha-cholest-7-en-3 beta-ol was also isolated and characterized as a product of the metabolism of the labeled delta 8(14)-15-ketosterol. The demonstration of the enzymatic conversion of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one to cholesterol in liver preparations suggests that previous estimates of the biological potency of this compound may be much lower than the true values and/or that metabolites of this compound may be the active species responsible for its biological actions.