15-Oxygenated sterols with the unnatural cis-C-D ring junction. Studies of the metabolism of 5 alpha,14 beta-cholest-7-ene-3 beta,15 alpha-diol and 5 alpha,14 beta-cholest-7-ene-3 beta,15 beta-diol.

Four 15-oxygenated sterols with the "unnatural" cis-C-D ring juncture have recently been shown to be potent inhibitors of sterol synthesis in animal cells in culture (Schroepfer, G.J., Jr., Parish, E.J., Chen, H.W., and Kandutsch, A.A. (1977) J. Biol. Chem. 252, 8975-8980; Schroepfer, G.J., Jr., Pascal, R.A., Jr., and Kandutsch, A.A. (1979) Biochem. Pharmacol. 28, 249-252). In the present study we have prepared two of these sterols, [2,4-3H]5 alpha,14 beta-cholest-7-ene-3 beta,15 alpha-diol and [2,4-3H]5 alpha,14 beta-cholest-7-ene-3 beta,15 beta-diol, in labeled form, 5 alpha,14 beta-Cholest-7-ene-3 beta, 15 alpha-diol, but not its 15 beta-hydroxy epimer, was shown to be efficiently converted to cholesterol in 10,000 x g supernatant fractions of liver homogenate preparations from both male and female rats. After incubation of [2,4-3H]5 alpha,14 beta-cholest-7-ene-3 beta,15 alpha-diol with these enzyme preparations a number of labeled products, in addition to cholesterol, were isolated and characterized. These included 5 alpha-cholesta-8,14-dien-3 beta-ol, cholesta-5,7-dien-3 beta-ol, 5 alpha-cholest-8-en-3 beta-ol, and 5 alpha-cholest-7-en-3 beta-ol. A scheme to account for the enzymatic formation of cholesterol and the other sterol precursors of cholesterol is presented.