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

Sui Min Qiu, Gary Wen, Nobuyuki Hirakawa, Roger D. Soloway, Nan Kang Hong, Roger S. Crowther

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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 diminished by increasing glycochenodeoxycholic acid concentrations, and this relationship was interpreted as competition between bile acid and HPO42- 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.

Original languageEnglish (US)
Pages (from-to)1265-1271
Number of pages7
JournalJournal of Clinical Investigation
Volume88
Issue number4
DOIs
StatePublished - 1991

Keywords

  • Bile salts
  • Biomineralization
  • Calcification
  • Fourier transform infrared spectroscopy
  • Gallstones

ASJC Scopus subject areas

  • Medicine(all)

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