Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Apr;84(7):2052–2056. doi: 10.1073/pnas.84.7.2052

Transport of conjugated bilirubin and other organic anions in bile: relation to biliary lipid structures.

S Tazuma, R T Holzbach
PMCID: PMC304582  PMID: 3470776

Abstract

Using gel-permeation chromatography, we studied associative relationships between conjugated bilirubin and various biliary lipid particle species, including lecithin/cholesterol vesicles, mixed-lipid micelles, and simple bile salt micelles. Five other organic anions were comparably studied: phenol red, Evans blue, sulfobromophthalein, rose bengal, and indocyanine green. For compounds of intermediate hydrophobicity, including conjugated bilirubin, the dominant association was with a bile salt/organic anion hybrid particle of dimensions larger than that of a simple pure bile salt micelle. Vesicular association was found to be dominant only for the most hydrophobic organic anions, indocyanine green and rose bengal; conversely, the most hydrophilic anion, phenol red, showed no vesicular association. Accordingly, a strong positive correlation (P less than 0.001) was found between percent vesicular association and degree of hydrophobicity of the organic anion. Alkaline conditions (eluant pH 9) decreased or prevented vesicular hydrophobic interaction with all anions. We conclude that two important particulate mechanisms for transport in bile of conjugated bilirubin and other water-soluble anions are bile salt/organic anion hybrid particles and vesicles. For most organic anions of intermediate hydrophobicity, including conjugated bilirubin, the bile salt/organic anion hybrid particle is the dominant transport vehicle.

Full text

PDF
2052

Selected References

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

  1. Barrett P. V., Mullins F. X., Berlin N. I. Studies on the biosynthesis production of bilirubin-C14: an improved method utilizing delta-aminolevulinic acid-4-C14 in dogs. J Lab Clin Med. 1966 Dec;68(6):905–912. [PubMed] [Google Scholar]
  2. Boyer J. L., Scheig R. L., Klatskin G. The effect of sodium taurocholate on the hepatic metabolism of sulfobromophthalein sodium (BSP). The role of bile flow. J Clin Invest. 1970 Feb;49(2):206–215. doi: 10.1172/JCI106229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gordon E. R., Chan T. H., Samodai K., Goresky C. A. The isolation and further characterization of the bilirubin tetrapyrroles in bile-containing human duodenal juice and dog gall-bladder bile. Biochem J. 1977 Oct 1;167(1):1–8. doi: 10.1042/bj1670001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Goresky C. A., Haddad H. H., Kluger W. S., Nadeau B. E., Bach G. G. The enhancement of maximal bilirubin excretion with taurocholate-induced increments in bile flow. Can J Physiol Pharmacol. 1974 Jun;52(3):389–403. doi: 10.1139/y74-055. [DOI] [PubMed] [Google Scholar]
  5. Halpern Z., Dudley M. A., Kibe A., Lynn M. P., Breuer A. C., Holzbach R. T. Rapid vesicle formation and aggregation in abnormal human biles. A time-lapse video-enhanced contrast microscopy study. Gastroenterology. 1986 Apr;90(4):875–885. doi: 10.1016/0016-5085(86)90863-2. [DOI] [PubMed] [Google Scholar]
  6. Holzbach R. T., Kibe A., Thiel E., Howell J. H., Marsh M., Hermann R. E. Biliary proteins. Unique inhibitors of cholesterol crystal nucleation in human gallbladder bile. J Clin Invest. 1984 Jan;73(1):35–45. doi: 10.1172/JCI111204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. JUNIPER K., Jr PHYSICOCHEMICAL CHARACTERISTICS OF BILE AND THEIR RELATION TO GALLSTONE FORMATION. Am J Med. 1965 Jul;39:98–107. doi: 10.1016/0002-9343(65)90249-4. [DOI] [PubMed] [Google Scholar]
  8. Kibe A., Dudley M. A., Halpern Z., Lynn M. P., Breuer A. C., Holzbach R. T. Factors affecting cholesterol monohydrate crystal nucleation time in model systems of supersaturated bile. J Lipid Res. 1985 Sep;26(9):1102–1111. [PubMed] [Google Scholar]
  9. Mazer N. A., Carey M. C. Quasi-elastic light-scattering studies of aqueous biliary lipid systems. Cholesterol solubilization and precipitation in model bile solutions. Biochemistry. 1983 Jan 18;22(2):426–442. doi: 10.1021/bi00271a029. [DOI] [PubMed] [Google Scholar]
  10. Mazer N. A., Schurtenberg P., Carey M. C., Preisig R., Weigand K., Känzig W. Quasi-elastic light scattering studies of native hepatic bile from the dog: comparison with aggregative behavior of model biliary lipid systems. Biochemistry. 1984 Apr 24;23(9):1994–2005. doi: 10.1021/bi00304a018. [DOI] [PubMed] [Google Scholar]
  11. Mok H. Y., Von Bergmann K., Grundy S. M. Kinetics of the enterohepatic circulation during fasting: biliary lipid secretion and gallbladder storage. Gastroenterology. 1980 May;78(5 Pt 1):1023–1033. [PubMed] [Google Scholar]
  12. Nakayama F. Nature of cholesterol-complexing macromolecular fractions in bile. Clin Chim Acta. 1966 Feb;13(2):212–220. doi: 10.1016/0009-8981(66)90295-6. [DOI] [PubMed] [Google Scholar]
  13. O'Máille E. R., Richards T. G., Short A. H. Factors determining the maximal rate of organic anion secretion by the liver and further evidence on the hepatic site of action of the hormone secretin. J Physiol. 1966 Oct;186(2):424–438. doi: 10.1113/jphysiol.1966.sp008044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pattinson N. R., Chapman B. A. Distribution of biliary cholesterol between mixed micelles and nonmicelles in relation to fasting and feeding in humans. Gastroenterology. 1986 Sep;91(3):697–702. doi: 10.1016/0016-5085(86)90641-4. [DOI] [PubMed] [Google Scholar]
  15. Pattinson N. R. Solubilisation of cholesterol in human bile. FEBS Lett. 1985 Feb 25;181(2):339–342. doi: 10.1016/0014-5793(85)80288-x. [DOI] [PubMed] [Google Scholar]
  16. Pope J. L. Crystallization of sodium taurocholate. J Lipid Res. 1967 Mar;8(2):146–147. [PubMed] [Google Scholar]
  17. Reuben A., Howell K. E., Boyer J. L. Effects of taurocholate on the size of mixed lipid micelles and their associations with pigment and proteins in rat bile. J Lipid Res. 1982 Sep;23(7):1039–1052. [PubMed] [Google Scholar]
  18. Scharschmidt B. F., Schmid R. The micellar sink: a quantitative assessment of the association of organic anions with mixed micelles and other macromolecular aggregates in rat bile. J Clin Invest. 1978 Dec;62(6):1122–1131. doi: 10.1172/JCI109231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Shull S. D., Wagner C. I., Trotman B. W., Soloway R. D. Factors affecting bilirubin excretion in patients with cholesterol or pigment gallstones. Gastroenterology. 1977 Apr;72(4 Pt 1):625–629. [PubMed] [Google Scholar]
  20. Somjen G. J., Gilat T. A non-micellar mode of cholesterol transport in human bile. FEBS Lett. 1983 Jun 13;156(2):265–268. doi: 10.1016/0014-5793(83)80510-9. [DOI] [PubMed] [Google Scholar]
  21. Spivak W., Carey M. C. Reverse-phase h.p.l.c. separation, quantification and preparation of bilirubin and its conjugates from native bile. Quantitative analysis of the intact tetrapyrroles based on h.p.l.c. of their ethyl anthranilate azo derivatives. Biochem J. 1985 Feb 1;225(3):787–805. doi: 10.1042/bj2250787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sömjen G. J., Gilat T. Contribution of vesicular and micellar carriers to cholesterol transport in human bile. J Lipid Res. 1985 Jun;26(6):699–704. [PubMed] [Google Scholar]
  23. Tipping E., Ketterer B., Christodoulides L. Interactions of small molecules with phospholipid bilayers. Binding to egg phosphatidylcholine of some organic anions (bromosulphophthalein, oestrone sulphate, haem and bilirubin) that bind to ligandin and aminoazo-dye-binding protein A. Biochem J. 1979 May 15;180(2):327–337. doi: 10.1042/bj1800327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. VERSCHURE J. C., MIJNLIEFF P. F. The dominating macromolecular complex of human gallbladder bile. Clin Chim Acta. 1956 Mar;1(2):154–166. doi: 10.1016/0009-8981(56)90031-6. [DOI] [PubMed] [Google Scholar]
  25. Vonk R. J., Jekel P., Meijer D. K. Choleresis and hepatic transport mechanisms. II. Influence of bile salt choleresis and biliary micelle binding on biliary excretion of various organic anions. Naunyn Schmiedebergs Arch Pharmacol. 1975;290(4):375–387. doi: 10.1007/BF00499950. [DOI] [PubMed] [Google Scholar]
  26. Ware A. J., Carey M. C., Combes B. Solution properties of sulfobromophthalein sodium (BSP) compounds alone and in association with sodium taurocholate (TC). J Lab Clin Med. 1976 Mar;87(3):443–456. [PubMed] [Google Scholar]
  27. Wolkoff A. W., Scharschmidt B. F., Plotz P. H., Berk P. D. Purification of conjugated bilirubin: a new approach utilizing albumin-agarose gel affinity chromatography. Proc Soc Exp Biol Med. 1976 May;152(1):20–23. doi: 10.3181/00379727-152-39318. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES