Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1976 Feb 15;154(2):507–516. doi: 10.1042/bj1540507

Identification of bile acids in the serum and urine in cholestasis. Evidence for 6alpha-hydroxylation of bile acids in man.

J A Summerfield, B H Billing, C H Shackleton
PMCID: PMC1172731  PMID: 938463

Abstract

In this qualitative study of the pattern of bile acid excretion in cholestasis, methods are described for the isolation of bile acids from large volumes of urine and plasma. The bile acids were subjected to a group separation and identified by combined gas chromatography-mass spectrometry. The techniques were developed to allow identification of the minor components of the bile acid mixture. Four bile acids that have not previously been described in human urine and plasma were detected, namely 3beta, 7alpha-dihydroxy-5beta-cholan-24-oic acid, 3alpha, 6alpha-dihydroxy-5beta-cholan-24-oic acid (hyodeoxycholic acid), 3alpha, 6alpha, 7alpha-trihydroxy-5beta-cholan-24-oic acid (hyocholic acid) and 3alpha, 7beta, 12alpha-trihydroxy-5beta-cholan-24-oic acid. In addition three C27 steroids were found; 26-hydroxycholesterol and a trihydroxy cholestane, probably 5 beta-cholestane-3alpha, 7alpha, 26-triol were found in the sulphate fraction of plasma and urine. In the plasma sample, a sulphate conjugate of 24-hydroxycholesterol was found. The presence of these compounds probably reflects the existence of further pathways for bile acid metabolism. It is not yet known whether this is a consequence of the cholestasis or whether they are also present in normal man, at much lower concentrations.

Full text

PDF
507

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. Back P. Identification and quantitative determination of urinary bile acids excreted in cholestasis. Clin Chim Acta. 1973 Mar 14;44(2):199–207. doi: 10.1016/0009-8981(73)90382-3. [DOI] [PubMed] [Google Scholar]
  3. Back P. Synthesis and excretion of bile acids in a case of extrahepatic biliary atresia. Helv Med Acta. 1973 Sep;37(2):193–200. [PubMed] [Google Scholar]
  4. Björkhem I., Einarsson K., Hellers G. Metabolism of mono- and dihydroxylated bile acids in preparations of human liver. Eur J Clin Invest. 1973 Dec;3(6):459–465. doi: 10.1111/j.1365-2362.1973.tb02215.x. [DOI] [PubMed] [Google Scholar]
  5. Bradlow H. L. Extraction of steroid conjugates with a neutral resin. Steroids. 1968 Mar;11(3):265–272. doi: 10.1016/s0039-128x(68)80139-4. [DOI] [PubMed] [Google Scholar]
  6. Carey J. B., Jr, Williams G. Lithocholic acid in human-blood serum. Science. 1965 Oct 29;150(3696):620–622. doi: 10.1126/science.150.3696.620. [DOI] [PubMed] [Google Scholar]
  7. Eneroth P., Gordon B., Ryhage R., Sjövall J. Identification of mono- and dihydroxy bile acids in human feces by gas-liquid chromatography and mass spectrometry. J Lipid Res. 1966 Jul;7(4):511–523. [PubMed] [Google Scholar]
  8. Gregg J. A. Presence of bile acids in jaundiced human urine. Nature. 1967 Apr 1;214(5083):29–31. doi: 10.1038/214029a0. [DOI] [PubMed] [Google Scholar]
  9. Gustafsson J. A., Sjövall J. Identification of 22-, 24- and 26-hydroxycholesterol in the steroid sulphage fraction of faeces from infants. Eur J Biochem. 1969 Apr;8(4):467–472. doi: 10.1111/j.1432-1033.1969.tb00550.x. [DOI] [PubMed] [Google Scholar]
  10. Hirofuji S. Stero-bile acids and bile sterols. LXXII. Fecal bile acids in the dog. J Biochem. 1965 Jul;58(1):27–33. doi: 10.1093/oxfordjournals.jbchem.a128160. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Makino I., Sjövall J., Norman A., Strandvik B. Excretion of 3beta-hydroxy-5-cholenoic and 3a-hydroxy-5a-cholanoic acids in urine of infants with biliary atresia. FEBS Lett. 1971 Jun 10;15(2):161–164. doi: 10.1016/0014-5793(71)80047-9. [DOI] [PubMed] [Google Scholar]
  13. Mitropoulos K. A., Myant N. B. The formation of lithocholic acid, chenodeoxycholic acid and alpha- and beta-muricholic acids from cholesterol incubated with rat-liver mitochondria. Biochem J. 1967 May;103(2):472–479. doi: 10.1042/bj1030472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Murphy G. M., Billing B. H., Baron D. N. A fluorimetric and enzymatic method for the estimation of serum total bile acids. J Clin Pathol. 1970 Oct;23(7):594–598. doi: 10.1136/jcp.23.7.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Murphy G. M., Jansen F. H., Billing B. H. Unsaturated monohydroxy bile acids in cholestatic liver disease. Biochem J. 1972 Sep;129(2):491–494. doi: 10.1042/bj1290491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Norman A., Strandvik B. Formation and metabolism of bile acids in extrahepatic biliary atresia. J Lab Clin Med. 1971 Aug;78(2):181–193. [PubMed] [Google Scholar]
  17. Palmer R. H., Bolt M. G. Bile acid sulfates. I. Synthesis of lithocholic acid sulfates and their identification in human bile. J Lipid Res. 1971 Nov;12(6):671–679. [PubMed] [Google Scholar]
  18. SANDBERG D. H., SJOEVALL J., SJOEVALL K., TURNER D. A. MEASUREMENT OF HUMAN SERUM BILE ACIDS BY GAS-LIQUID CHROMATOGRAPHY. J Lipid Res. 1965 Apr;6:182–192. [PubMed] [Google Scholar]
  19. Shackleton C. H., Sjövall J., Wisén O. A simple method for the extraction of steroids from urine. Clin Chim Acta. 1970 Feb;27(2):354–356. doi: 10.1016/0009-8981(70)90357-8. [DOI] [PubMed] [Google Scholar]
  20. Trülzsch D., Roboz J., Greim H., Czygan P., Rudick J., Hutterer F., Schaffner F., Popper H. Hydroxylation of taurolithocholate by isolated human liver microsomes. I. Identification of metabolic product. Biochem Med. 1974 Feb;9(2):158–166. doi: 10.1016/0006-2944(74)90048-9. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES