Cholesterol 7α-Hydroxylase and 12α-Hydroxylase
- 379 Downloads
Three major cytochrome P450 enzymes are involved in the conversion of cholesterol into bile acids, i.e., cholesterol 7α-hydroxylase (EC 184.108.40.206), 12α-hydroxylase and 5β-cholestane-3α,7α,12α-triol 27-hydroxylase (EC 220.127.116.11) of which cholesterol 7α-hydroxylase catalyzes a rate-limiting step for overall conversion, whereas 12α-hydroxylase seems to regulate the relative amount of cholic acid over chenodeoxycholic acid (Björkhem 1985). 27-Hydroxylase catalyzes the hydroxylation of one of the terminal methyl groups of 5β-cholestane-3α,7α,12α-triol and 5β-cholestane-3α,7α-diol. In this chapter cholesterol 7α-hydroxylase and 12α-hydroxylase are reviewed. These two hydroxylases modify the steroid nucleus (Fig. 1). The cytochrome P450 species involved in side chain oxidation is reviewed elsewhere in this book by Wikvall (see Chap. 46).
KeywordsBile Acid Cholic Acid Chenodeoxycholic Acid Amino Glutethimide Cytochrome P450 Gene
Unable to display preview. Download preview PDF.
- Ali SS, Elliot WH (1971) Bile acids. LI. Formation of 12α-hydroxyl derivatives and companions from 5α-sterols by rabbit liver microsomes. J Lipid Res 17: 386–392Google Scholar
- Bernhardsson C, Björkhem I, Danielsson H (1973) 12α-Hydroxylation of 7α-hydroxy-4-cholesten-3-one by a reconstituted system from rat. Biochem Biophys Res Commun 54: 1030–1038Google Scholar
- Björkhem I, Danielsson H, Gustafsson J-A (1973) 7α-Hydroxylation of cholesterol by reconstituted systems from rat liver microsomes. FEBS Lett 31: 20–22Google Scholar
- Björkhem I, Danielsson H, Wikvall K (1974) 7α-Hydroxylation of cholesterol by reconstituted systems from rat liver microsomes. Biochem Biophys Res Commun 61: 934–941Google Scholar
- Hylemon PB, Heuman DM, Pandak WM, Chiang JYL, Vlahcevic ZR (1991) Proceedings of the 9th Nobel conference on biosynthesis, regulation and products of the mevalonate pathway; Sodergarn, Sweden, 2–5 June 1991 (in press)Google Scholar
- Kalles I, Wikvall (1981) Role of sulfhydryl groups in catalytic activity of purified cholesterol 7α-hydroxylase system from rabbit and rat liver microsomes. Biochem Biophys Res Commun 100: 1361–1369Google Scholar
- Mitropoulos KA, Balasubramaniam S, Venkatesan S, Reeves BE A (1978) On the mechanism for the regulation of 3-hydroxyl-3-methylglutaryl-coenzyme A reductase, of cholesterol 7α-hydroxylase and acyl-coenzyme A:cholesterol acyltransferase by the free cholesterol. Biochim Biophys Acta 530: 99–111PubMedGoogle Scholar
- Okuda K, Atsuta Y, Murakami K, Wakeshima C (1980) In: Coon MJ, Conney AH, Estabrook RW, Gelboin HV, Gillette JR, O’Brien PJ (eds) Microsomes, drug oxidations, and chemical carcinogenesis, vol 2, Academic, New York, p 745–748Google Scholar
- Reinher E, Bjórkhem I, Angelin B, Ewerth S, Einarsson K (1989) Bile acid synthesis in humans: regulation of hepatic microsomal cholesterol 7α-hydroxylase. Gastroenterology 97: 1498–1505Google Scholar