Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1975 Mar;55(3):478–486. doi: 10.1172/JCI107954

Biosynthesis of bile acids in man. Hydroxylation of the C27-steroid side chain.

I Björkhem, J Gustafsson, G Johansson, B Persson
PMCID: PMC301775  PMID: 1117065

Abstract

The first step in the degradation of the steroid side chain during biosynthesis of bile acids from cholesterol in man was studied in microsomal and mitochondrial fraction of homogenate of livers from 14 patients. The microsomal fraction was found to catalyze an efficient 25-hydroxylation of 5,8-cholestane-3a,7a,12atriol. A small extent of 23-, 24-, and 26-hydroxylation of the same substrate was observed. 53-Cholestane-3a,7adiol was hydroxylated in the 25-position only to a very small extent. The mitochondrial fraction was found to catalyze 26-hydroxylation of cholesterol, 5-cholestene-3P,7a-diol, 5P-cholestane-3a,7a-diol, 7a-hydroxy-4-cholesten-3-one, and 5,0-cholestane-3a,7a,12a-triol. Addition of Mg++ stimulated the 26-hydroxylation of cholesterol but had no effect or an inhibitory effect on 26-hydroxylation of the other substrates, indicating a heterogeneity of the mitochondrial 26-hydroxylating system. The level of 26-hydroxylase activity towards different substrates varied considerably with different mitochondrial preparations. The roles of the microsomal and mitochondrial 26- hydroxylations as well as the microsomal 25-hydroxylation in biosynthesis of bile acids in man are discussed. The results indicate that microsomal 26-hydroxylation is less important than mitochondrial 26-hydroxylation under normal conditions. The possibility that microsomal 25-hydroxylation is important cannot be ruled out.

Full text

PDF
485

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson K. E., Kok E., Javitt N. B. Bile acid synthesis in man: metabolism of 7 -hydroxycholesterol- 14 C and 26-hydroxycholesterol- 3 H. J Clin Invest. 1972 Jan;51(1):112–117. doi: 10.1172/JCI106780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Björkheim I., Danielsson H., Einarsson K., Johansson G. Formation of bile acids in man: conversion of cholesterol into 5-beta-cholestane-3-alpha, 7-alpha, 12-alpha-triol in liver homogenates. J Clin Invest. 1968 Jul;47(7):1573–1582. doi: 10.1172/JCI105849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Björkhem I., Danielsson H., Einarsson K. On the conversion of cholesterol to 5-beta-cholestane-3-alpha, 7-alpha-diol in guinea pig liver homogenates. Eur J Biochem. 1967 Oct;2(3):294–302. doi: 10.1111/j.1432-1033.1967.tb00138.x. [DOI] [PubMed] [Google Scholar]
  4. Björkhem I., Danielsson H., Gustafsson J. On the effect of thyroid hormone on 26-hydroxylation of C 27 -steroids in rat liver. FEBS Lett. 1973 Apr 1;31(1):20–22. doi: 10.1016/0014-5793(73)80064-x. [DOI] [PubMed] [Google Scholar]
  5. Björkhem I., Gustafsson J. Mitochondrial omega-hydroxylation of cholesterol side chain. J Biol Chem. 1974 Apr 25;249(8):2528–2535. [PubMed] [Google Scholar]
  6. Björkhem I., Gustafsson J. Omega-hydroxylation of steriod side-chain in biosynthesis of bile acids. Eur J Biochem. 1973 Jul 2;36(1):201–212. doi: 10.1111/j.1432-1033.1973.tb02902.x. [DOI] [PubMed] [Google Scholar]
  7. CAREY J. B., Jr CONVERSION OF CHOLESTEROL TO TRIHYDROXYCOPROSTANIC ACID AND CHOLIC ACID IN MAN. J Clin Invest. 1964 Jul;43:1443–1448. doi: 10.1172/JCI105020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cronholm T., Johansson G. Oxidation of 5 beta-cholestane-3alpha, 7alpha, 12alpha-triol by rat liver microsomes. Eur J Biochem. 1970 Oct;16(2):373–381. doi: 10.1111/j.1432-1033.1970.tb01091.x. [DOI] [PubMed] [Google Scholar]
  9. ENEROTH P. THIN-LAYER CHROMATOGRAPHY OF BILE ACIDS. J Lipid Res. 1963 Jan;4:11–16. [PubMed] [Google Scholar]
  10. Eneroth P., Gustafsson J. -A. Steroids in newborns and infants. Hydroxylated cholesterol derivatives in the steroid monosulphate fraction from meconium. FEBS Lett. 1969 Apr;3(2):129–132. doi: 10.1016/0014-5793(69)80115-8. [DOI] [PubMed] [Google Scholar]
  11. HELLSTROEM K., LINDSTEDT S. CHOLIC-ACID TURNOVER AND BILIARY BILE-ACID COMPOSITION IN HUMANS WITH ABNORMAL THYROID FUNCTION. BILE ACIDS AND STEROIDS 139. J Lab Clin Med. 1964 Apr;63:666–679. [PubMed] [Google Scholar]
  12. Hanson R. F. The formation and metabolism of 3 ,7 -dihydroxy-5 -cholestan-26-oic acid in man. J Clin Invest. 1971 Oct;50(10):2051–2055. doi: 10.1172/JCI106698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  14. MAKITA M., WELLS W. W. Quantitative analysis of fecal bile acids by gas-liquid chromatography. Anal Biochem. 1963 Jun;5:523–530. doi: 10.1016/0003-2697(63)90072-1. [DOI] [PubMed] [Google Scholar]
  15. STAPLE E., RABINOWITZ J. L. Formation of trihydroxycoprostanic acid from cholesterol in man. Biochim Biophys Acta. 1962 Jun 4;59:735–736. doi: 10.1016/0006-3002(62)90663-7. [DOI] [PubMed] [Google Scholar]
  16. Setoguchi T., Salen G., Tint G. S., Mosbach E. H. A biochemical abnormality in cerebrotendinous xanthomatosis. Impairment of bile acid biosynthesis associated with incomplete degradation of the cholesterol side chain. J Clin Invest. 1974 May;53(5):1393–1401. doi: 10.1172/JCI107688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Taniguchi S., Hoshita N., Okuda K. Enzymatic characteristics of CO-sensitive 26-hydroxylase system for 5beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol in rat-liver mitochondria and its intramitochondrial localization. Eur J Biochem. 1973 Dec 17;40(2):607–617. doi: 10.1111/j.1432-1033.1973.tb03233.x. [DOI] [PubMed] [Google Scholar]
  18. WHITEHOUSE M. W., STAPLE E., GURIN S. Catabolism in vitro of cholesterol. II. Further studies on the oxidation of cholesterol by rat liver mitochondria. J Biol Chem. 1961 Jan;236:68–72. [PubMed] [Google Scholar]
  19. Yamada T. Stero-bile acids and bile alcohols. 93. Metabolism of 5-beta-cholestane-3-alpha, 7-alpha, 12-alpha, 25-tetrol. Hiroshima J Med Sci. 1966 Dec;15(4):375–390. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES