出版社：American Society for Biochemistry and Molecular Biology
摘要：Structurally closely related steroids have been tested as substrates for the NADPH-dependent cholesterol-and cholestanol-7 alpha-hydroxylase(s) considered to be the rate-limiting enzyme(s) in bile acid biosynthesis. Of the steroids tested, 5-cholesten-3 alpha-0l, 5 alpha-cholestan-3 alpha-ol, 5 beta-cholestan-3 alpha-ol, 5 beta-cholestan-3 beta-ol, 4-cholesten-3 alpha-ol, 4-cholesten-3 beta-ol, 5 alpha-cholestan-3-one, 5 beta-cholestan-3-one, 24 alpha-methylcholesterol and the 24 alpha-ethyl derivatives of cholestanol, 5 beta-cholestan-3 alpha-ol, 5 beta-cholestan-3 beta-ol, and 4-cholesten-3-one, only 4-cholesten-3 beta-ol was 7 alpha-hydroxylated to a significant extent (approximately 1/5 of the conversion of exogenous cholesterol). This suggests that the 7 alpha-hydroxylase(s) is sensitive to the structure of the side chain, and that it requires a rather flat steroid nucleus (delta4-, delta5-, or 5 alpha-steroid) and an equatorial or quasiequatorial hydroxyl group at C3. The nature of the 7 alpha-hydroxylation is discussed and the importance of the beta-side of the steroid molecule is emphasized. Minute amounts of the 7 beta-hydroxy derivatives were formed from 4-cholesten-3 beta-ol, 5 beta-cholestan-3 alpha-ol, 24 alpha-ethyl-5 beta-cholestan-3 alpha-ol and, probably, from 5 beta-cholestan-3 beta-ol and 24 alpha-ethyl-5 beta-cholestan-3 beta-ol.
