Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 Oct;88(4):1265–1271. doi: 10.1172/JCI115430

Glycochenodeoxycholic acid inhibits calcium phosphate precipitation in vitro by preventing the transformation of amorphous calcium phosphate to calcium hydroxyapatite.

S M Qiu 1, G Wen 1, N Hirakawa 1, R D Soloway 1, N K Hong 1, R S Crowther 1
PMCID: PMC295595  PMID: 1655828

Abstract

Calcium hydroxyapatite can be a significant component of black pigment gallstones. Diverse molecules that bind calcium phosphate inhibit hydroxyapatite precipitation. Because glycine-conjugated bile acids, but not their taurine counterparts, bind calcium phosphate, we studied whether glycochenodeoxycholic acid inhibits calcium hydroxyapatite formation. Glycochenodeoxycholic acid (2 mM) totally inhibited transformation of amorphous calcium phosphate microprecipitates to macroscopic crystalline calcium hydroxyapatite. This inhibition was not mediated by decreased Ca2+ activity. Taurocholic acid (2-12 mM) did not affect hydroxyapatite formation, but antagonized glycochenodeoxycholic acid. Both amorphous and crystalline precipitates contained a surface fraction relatively rich in phosphate. The surface phosphate content was diminish by increasing glycochenodeoxycholic acid concentrations, and this relationship was interpreted as competition between bile acid and HPO4(-4) for binding sites on the calcium phosphate surface. A phosphate-rich crystal surface was associated with rapid transition from amorphous to crystalline states. These results indicate that glycochenodeoxycholic acid prevents transformation of amorphous calcium phosphate to crystalline hydroxyapatite by competitively inhibiting the accumulation of phosphate on the crystal embryo surface.

Full text

PDF
1265

Selected References

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

  1. Angelico M., De Sanctis S. C., Gandin C., Alvaro D. Spontaneous formation of pigmentary precipitates in bile salt-depleted rat bile and its prevention by micelle-forming bile salts. Gastroenterology. 1990 Feb;98(2):444–453. doi: 10.1016/0016-5085(90)90837-q. [DOI] [PubMed] [Google Scholar]
  2. Blumenthal N. C., Posner A. S., Silverman L. D., Rosenberg L. C. Effect of proteoglycans on in vitro hydroxyapatite formation. Calcif Tissue Int. 1979 Mar 13;27(1):75–82. doi: 10.1007/BF02441164. [DOI] [PubMed] [Google Scholar]
  3. Chattopadhyay A., London E. Fluorimetric determination of critical micelle concentration avoiding interference from detergent charge. Anal Biochem. 1984 Jun;139(2):408–412. doi: 10.1016/0003-2697(84)90026-5. [DOI] [PubMed] [Google Scholar]
  4. Cheng P. T., Pritzker K. P. Solution Ca/P ratio affects calcium phosphate crystal phases. Calcif Tissue Int. 1983 Jul;35(4-5):596–601. doi: 10.1007/BF02405100. [DOI] [PubMed] [Google Scholar]
  5. Crowther R. S., Soloway R. D. Pigment gallstone pathogenesis: from man to molecules. Semin Liver Dis. 1990 Aug;10(3):171–180. doi: 10.1055/s-2008-1040471. [DOI] [PubMed] [Google Scholar]
  6. Eanes E. D., Meyer J. L. The maturation of crystalline calcium phosphates in aqueous suspensions at physiologic pH. Calcif Tissue Res. 1977 Oct 20;23(3):259–269. doi: 10.1007/BF02012795. [DOI] [PubMed] [Google Scholar]
  7. Eanes E. D., Termine J. D., Nylen M. U. An electron microscopic study of the formation of amorphous calcium phosphate and its transformation to crystalline apatite. Calcif Tissue Res. 1973 May 9;12(2):143–158. doi: 10.1007/BF02013730. [DOI] [PubMed] [Google Scholar]
  8. FLEISCH H., BISAZ S. Isolation from urine of pyrophosphate, a calcification inhibitor. Am J Physiol. 1962 Oct;203:671–675. doi: 10.1152/ajplegacy.1962.203.4.671. [DOI] [PubMed] [Google Scholar]
  9. Lichtenberg D., Werker E., Bor A., Almog S., Nir S. Precipitation of calcium palmitate from bile salt-containing dispersions. Chem Phys Lipids. 1988 Oct;48(3-4):231–243. doi: 10.1016/0009-3084(88)90093-x. [DOI] [PubMed] [Google Scholar]
  10. Moore E. W., Celic L., Ostrow J. D. Interactions between ionized calcium and sodium taurocholate: bile salts are important buffers for prevention of calcium-containing gallstones. Gastroenterology. 1982 Nov;83(5):1079–1089. [PubMed] [Google Scholar]
  11. Nancollas G. H. Crystallization in bile. Hepatology. 1984 Sep-Oct;4(5 Suppl):169S–172S. doi: 10.1002/hep.1840040832. [DOI] [PubMed] [Google Scholar]
  12. Roda A., Hofmann A. F., Mysels K. J. The influence of bile salt structure on self-association in aqueous solutions. J Biol Chem. 1983 May 25;258(10):6362–6370. [PubMed] [Google Scholar]
  13. Root M. J. Inhibition of the amorphous calcium phosphate phase transformation reaction by polyphosphates and metal ions. Calcif Tissue Int. 1990 Aug;47(2):112–116. doi: 10.1007/BF02555994. [DOI] [PubMed] [Google Scholar]
  14. Shimizu S., Sabsay B., Veis A., Ostrow J. D., Rege R. V., Dawes L. G. Isolation of an acidic protein from cholesterol gallstones, which inhibits the precipitation of calcium carbonate in vitro. J Clin Invest. 1989 Dec;84(6):1990–1996. doi: 10.1172/JCI114389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sutor D. J., Percival J. M. Presence or absence of inhibitors of crystal growth in bile. 1. Effect of bile on the formation of calcium phosphate, a constituent of gallstones. Gut. 1976 Jul;17(7):506–510. doi: 10.1136/gut.17.7.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Termine J. D., Conn K. M. Inhibition of apatite formation by phosphorylated metabolites and macromolecules. Calcif Tissue Res. 1976 Dec 22;22(2):149–157. doi: 10.1007/BF02010354. [DOI] [PubMed] [Google Scholar]
  17. Termine J. D., Eanes E. D. Comparative chemistry of amorphous and apatitic calcium phosphate preparations. Calcif Tissue Res. 1972;10(3):171–197. doi: 10.1007/BF02012548. [DOI] [PubMed] [Google Scholar]
  18. Termine J. D., Lundy D. R. Vibrational spectra of some phosphate salts amorphous to X-ray diffraction. Calcif Tissue Res. 1974 Jun 11;15(1):55–70. doi: 10.1007/BF02059043. [DOI] [PubMed] [Google Scholar]
  19. Termine J. D., Peckauskas R. A., Posner A. S. Calcium phosphate formation in vitro. II. Effects of environment on amorphous-crystalline transformation. Arch Biochem Biophys. 1970 Oct;140(2):318–325. doi: 10.1016/0003-9861(70)90072-x. [DOI] [PubMed] [Google Scholar]
  20. Tew W. P., Mahle C., Benavides J., Howard J. E., Lehninger A. L. Synthesis and characterization of phosphocitric acid, a potent inhibitor of hydroxylapatite crystal growth. Biochemistry. 1980 Apr 29;19(9):1983–1988. doi: 10.1021/bi00550a039. [DOI] [PubMed] [Google Scholar]
  21. Tung M. S., Brown W. E. An intermediate state in hydrolysis of amorphous calcium phosphate. Calcif Tissue Int. 1983 Sep;35(6):783–790. doi: 10.1007/BF02405124. [DOI] [PubMed] [Google Scholar]
  22. Van den Berg C. J., Hill L. F., Stanbury S. W. Inositol phosphates and phytic acid as inhibitors of biological calcification in the rat. Clin Sci. 1972 Sep;43(3):377–383. doi: 10.1042/cs0430377. [DOI] [PubMed] [Google Scholar]
  23. Van der Meer R., De Vries H. T. Differential binding of glycine- and taurine-conjugated bile acids to insoluble calcium phosphate. Biochem J. 1985 Jul 1;229(1):265–268. doi: 10.1042/bj2290265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. WOMACK N. A., ZEPPA R., IRVIN G. L., 3rd The anatomy of gallstones. Ann Surg. 1963 May;157:670–686. doi: 10.1097/00000658-196305000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. West V. C. Observations on phase transformation of a precipitated calcium phosphate. Calcif Tissue Res. 1971;7(3):212–219. doi: 10.1007/BF02062608. [DOI] [PubMed] [Google Scholar]
  26. Williams G., Sallis J. D. Structural factors influencing the ability of compounds to inhibit hydroxyapatite formation. Calcif Tissue Int. 1982 Mar;34(2):169–177. doi: 10.1007/BF02411229. [DOI] [PubMed] [Google Scholar]
  27. Williams G., Sallis J. D. Structure--activity relationship of inhibitors of hydroxyapatite formation. Biochem J. 1979 Oct 15;184(1):181–184. doi: 10.1042/bj1840181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wuthier R. E. Effect of phospholipids on the transformation of amorphous calcium phosphate to hydroxapatite in vitro. Calcif Tissue Res. 1975 Dec 22;19(3):197–210. doi: 10.1007/BF02564004. [DOI] [PubMed] [Google Scholar]

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

RESOURCES