Enzymatic formation and chemical synthesis of an active metabolite of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one, a potent regulator of cholesterol metabolism

• Published in: Biochemical and biophysical research communications Vol. 151; no. 1; p. 130
• Main Authors: Schroepfer, Jr, G J, Kim, H S, Vermilion, J L, Stephens, T W, Pinkerton, F D, Needleman, D H, Wilson, W K, St Pyrek, J
• Format: Journal Article
• Language: English
• Published: United States 29-02-1988
• Subjects: Animals; Cell Line; Chemical Phenomena; Chemistry; Cholestenes - biosynthesis; Cholestenes - chemical synthesis; Cholestenes - metabolism; Cholestenones - biosynthesis; Cholestenones - chemical synthesis; Cholestenones - metabolism; Cholesterol; Esters; Hydroxymethylglutaryl CoA Reductases - metabolism; Jejunum - metabolism; Microsomes - metabolism; Mitochondria, Liver - metabolism; Rats
• ISSN: 0006-291X
• DOI: 10.1016/0006-291X(88)90568-2

The enzymatic (rat liver mitochondria) conversion of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one to 5 alpha-cholest-8(14)-ene-3 beta,26-diol-15-one is described. The enzymatic product was judged, on the basis of IH and 13C NMR studies, to be a 4:1 mixture of its 25R and 25S isomers. (25R)-5 alpha-Cholest-8(14)-ene-3 beta,26-diol-15-one was prepared through a five-step synthesis from (25R)-26-hydroxycholesterol. The (25R) isomer of the new compound was found to be highly active in the suppression of the levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured mammalian cells and to inhibit the esterification of cholesterol in jejunal microsomes.