Characterisation of bile acid metabolism in man using bile acids labelled with stable isotopes

  • A. F. Hofmann
  • P. D. Klein


Bile acids are acidic steroids formed in the liver from cholesterol and secreted into bile as their N-glycine or N-taurine conjugates. Their biological and clinical aspects have been thoroughly reviewed (Heaton, 1972; Dietschy, 1972; Nair and Kritchevsky, 1973; Paumgartner, 1977). Bile acids are amphipathic molecules which can disperse lecithin in micellar form, and bile is a concentrated micellar solution containing mixed micelles of bile acids, lecithin and cholesterol. When this mixed bile acid micelle reaches the small intestinal lumen, its composition changes and now the major lipid constituting the mixed micelle is fatty acid (plus some monoglyceride), which derives from pancreatic lipolysis of dietary triglyceride. Micellar solubilisation of the relatively insoluble fatty acid and monoglyceride greatly increases their aqueous concentration and thus accelerates the diffusive flux through the unstirred layer. Most of the bile acids are reabsorbed in the small intestine, especially the terminal ileum, where there is an active transport site. The bile acids return in the portal blood to the liver, where they are efficiently extracted and rapidly secreted into bile. This circulation of bile acids from liver to intestine and back to liver is termed the enterohepatic circulation, and it occurs about twice per meal. A small amount of bile acids are lost from the enterohepatic circulation and are excreted in faeces; the bile acid pool is maintained by hepatic synthesis. There is no urinary loss of bile acids (Figure 17.1). The bile acid conjugates are mostly absorbed in conjugated form from the small intestine, but a small amount of the bile acid conjugates is hydrolysed by bacterial deconjugases, releasing the unconjugated bile acid moiety. Most of this is reabsorbed to return to the liver, where it is reconjugated (Hepner et al., 1973).


Bile Acid Chenodeoxycholic Acid Enterohepatic Circulation Lithocholic Acid Bile Acid Metabolism 
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  1. Allan, R. N., Thistle, J. L. and Hofmann, A. F. (1976). Gut, 17, 413CrossRefGoogle Scholar
  2. Balistreri, W. F., Cowen, A. E., Hofmann, A. F., Szczepanik, P. A. and Klein, P. D. (1975). J. Ped. Res., 9, 757CrossRefGoogle Scholar
  3. Bennion, L. J. and Grundy, S. M. (1975). J. Clin. Invest., 56, 996CrossRefGoogle Scholar
  4. Bergström, S., Rottenberg, M. and Voltz, J. (1953). Acta Chem. Scand., 7, 481CrossRefGoogle Scholar
  5. Chavez, M. N. and Krone, C. L. (1976). J. Lipid Res., 17, 545Google Scholar
  6. Cowen, A. E., Korman, M. G., Hofmann, A. F., Cass, O. W. and Coffin, S. B. (1975). Gastroenterology, 69, 67Google Scholar
  7. Dietschy, J. M. (1972). Arch. Intern. Med., 130, 473CrossRefGoogle Scholar
  8. Fromm, H. and Hofmann, A. F. (1971). Lancet, 2, 621CrossRefGoogle Scholar
  9. Hachey, D. L., Szczepanik, P. A., Berngruber, O. W. and Klein, P. D. (1974). J. Labelled Comp., 9, 703CrossRefGoogle Scholar
  10. Heaton, K. W. (1972). Bile Salts in Health and Disease, Williams and Wilkins, Baltimore, p. 252Google Scholar
  11. Hepner, G. W., Hofmann, A. F. and Thomas, P. J. (1972a). J. Clin. Invest., 51, 1889CrossRefGoogle Scholar
  12. Hepner, G. W., Hofmann, A. F. and Thomas, P. J. (1972b). J. Clin. Invest., 51, 1898CrossRefGoogle Scholar
  13. Hepner, G. W., Sturman, J. A., Hofmann, A. F. and Thomas, P. J. (1973). J. Clin. Invest., 52, 433CrossRefGoogle Scholar
  14. Hepner, G. W. and Vessel, E. S. (1974). N. Engl. J. Med., 291, 1384CrossRefGoogle Scholar
  15. Hoffman, N. E., LaRusso, N. F. and Hofmann, A. F. (1976). Mayo Clin. Proc., 51, 171Google Scholar
  16. Hofmann. A. F., Szczepanik, P. A. and Klein, P. D. (1968). J. Lipid Res., 9, 707Google Scholar
  17. Hofmann, A. F., Danzinger, R. G., Hoffman, N. E., Klein, P. D., Berngruber, O. W. and Szczepanik, P. A. (1972). Proc. Seminar on the Use of Stable Isotopes in Clinical Pharmacology (ed. P. D. Klein and L. J. Roth), p. 37. National Technical Information Services Document CONF-711115Google Scholar
  18. Hofmann, A. F. and Hoffman, N. E. (1974). Gastroenterology, 67, 341Google Scholar
  19. Klein, P. D., Haumann, J. R. and Hachey, D. L. (1975). Clin. Chem., 21, 1253Google Scholar
  20. Lack, L., Dorrity, F. O., Jr., Walker, T. and Singletary, G. D. (1973). J. Lipid Res., 14, 367Google Scholar
  21. LaRusso, N. F., Hoffman, N. E. and Hofmann, A. F. (1974). J. Lab. Clin. Med., 84, 759Google Scholar
  22. Lauterburg, B. H. and Birchner, J. (1976). J. Pharmacol. Exp. Ther., 196, 501Google Scholar
  23. Lindstedt, S. (1957). Acta Physiol. Scand., 40, 1CrossRefGoogle Scholar
  24. Mede, K. A., Tserng, K. Y. and Klein, P. D. (1976). Gastroenterology, 71, 921 (abstract)Google Scholar
  25. Murphy, G. M., Edkins, S. M., Williams, J. W. and Catty, D. (1974). Clin. Chim. Acta, 54, 81CrossRefGoogle Scholar
  26. Nair, P. P. and Kritchevsky, D. (1973). The Bile Acids, Chemistry, Physiology, and Metabolism. Vol. II, Physiology and Metabolism, Plenum Press, New YorkCrossRefGoogle Scholar
  27. Newcomer, A. D., Thomas, P. J. and Hofmann, A. F. (1976) Gastroenterology, 70, 923 (abstract)Google Scholar
  28. Ng, P. Y., Allan, R. N. and Hofmann, A. F. (1977). J. Lipid Res. (in press)Google Scholar
  29. Norman, A. (1955). Arkiv Kemi, 8, 331Google Scholar
  30. Osuga, T., Mitamura, K., Mashige, F. and Imai, K. (1977). Clin. Chim. Acta, 75, 81CrossRefGoogle Scholar
  31. Palmer, R. H. (1969). Methods in Enzymology, Vol. XV, Steroids and Terpenoids (ed. S. P. Colowick and N. O. Kaplan), Academic Press, New York, p. 280Google Scholar
  32. Paumgartner, G. (1977). Clinics in Gastroenterology, Vol. 6, Saunders, LondonGoogle Scholar
  33. Salen, G., Tint, G. S., Eliav, B., Deering, N. and Mosbach, E. H. (1974). J. Clin. Invest., 53, 612CrossRefGoogle Scholar
  34. Schoeller, D. A., Schneider, J. F., Solomons, N. W., Watkins, J. B. and Klein, P. D. (1977). J. Lab. Clin. Med. (in press)Google Scholar
  35. Simmonds, W. J., Korman, M. G., Go, V. L. W. and Hofmann, A. F. (1973). Gastroenterology, 65, 705Google Scholar
  36. Solomon, N. W., Schoeller, D. A., Wagonfeld, J. B., Ott, D., Rosenberg, I. H. and Klein, P. D. (1977). J. Lab. Clin. Med. (in press)Google Scholar
  37. Thistle, J. L. and Hofmann, A. F. (1973). N. Engl. J. Med., 289, 655CrossRefGoogle Scholar
  38. Tserng, K. Y., Hachey, D. L. and Klein, P. D. (1977). J. Lipid Res. (in press)Google Scholar
  39. Tserng, K. Y. and Klein, P. D. (1977). J. Lipid Res. (in press)Google Scholar
  40. Vlahcevic, Z. R., Bell, C. C., Jr., Buhac, I., Farrar, J. T. and Swell, L. (1970). Gastroenterology, 59, 165Google Scholar
  41. Watkins, J. B., Ingall, D., Szczepanik, P. A., Klein, P. D. and Lester, R. (1973). N. Engl. J. Med., 288, 431CrossRefGoogle Scholar
  42. Watkins, J. B., Szczepanik, P. A., Gould, J., Klein, P. D. and Lester, R. (1975a). Gastroenterology, 69, 706Google Scholar
  43. Watkins, J. B., Tercyak, A. M., Szczepanik, P. A. and Klein, P. D. (1975b). Gastroenterology, 68, 1087 (abstract)Google Scholar

Copyright information

© The Contributors 1978

Authors and Affiliations

  • A. F. Hofmann
    • 1
    • 2
  • P. D. Klein
    • 1
    • 2
  1. 1.Gastroenterology Research UnitMayo Clinic and Mayo FoundationRochesterUSA
  2. 2.Division of Biological and Medical ResearchArgonne National LaboratoryArgonneUSA

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