Abstract
In this study, we compared in vitro calcium binding by the taurine and glycine conjugates of the major bile acids in human bile: cholic (CA), chenodeoxycholic (CDCA) and deoxycholic (DCA) acids, together with the cholelitholytic bile acids ursodeoxycholic (UDCA) and ursocholic (UCA) acids. At physiological total calcium (CaTOT) (1-15 mM) and bile acid (BA) (10-50 mM) concentrations, all the bile acids caused concentration-dependent falls in [Ca2+], suggesting calcium binding. Except for glycine-conjugated CDCA, all the other calcium-bile acid complexes were soluble in 150 mM NaCl. The calcium binding affinities followed the pattern: dihydroxy (CDCA, UDCA and DCA) greater than trihydroxy (CA and UCA) bile acids, and glycine conjugates greater than taurine conjugates. The glycine conjugate of UDCA, which increases during UDCA treatment, had the highest calcium binding affinity. Ten-20 mM phospholipid modestly increased calcium binding by CA conjugates, but not by CDCA, UDCA, and DCA conjugates. Phospholipid also prevented the precipitation of glyco-CDCA in the presence of calcium. Bile acid-calcium biding was pH-independent over the range 6.5-8.5. The different calcium binding affinities of the major biliary bile acids may partly explain their varying effects on biliary calcium secretion. The results also suggest that neither precipitation of calcium-bile acid complexes nor impaired calcium binding by bile acids is important in the pathogenesis of human calcium gallstone formation.
Highlights
In this study, we compared in vitro calcium binding by the taurine and glycine conjugates of the major bile acids in human bile: cholic (CA), chenodeoxycholic (CDCA) and deoxycholic (DCA) acids, together with the cholelitholytic bile acids unodeoxycholic (UDCA) and unocholic (UCA) acids
Similar concentration-dependent decreases in slope were seen with E A, glycocholic acid (GCA), TUDCA, GUDCA, taurodeoxycholic acid (TDCA), and GCDCA
Murphy, and Dowling Calcium binding by bile acids 783
Summary
We compared in vitro calcium binding by the taurine and glycine conjugates of the major bile acids in human bile: cholic (CA), chenodeoxycholic (CDCA) and deoxycholic (DCA) acids, together with the cholelitholytic bile acids unodeoxycholic (UDCA) and unocholic (UCA) acids. It) During ursodeoxycholic acid (UDCA) treatment, bile becomes enriched with the glycine conjugates of UDCA [15] and acquired gallstone calcification is common [16,17,18,19,20] The mechanism for this calcification may be increased carbonate ion concentration following UDCA-induced bicarbonate secretion by the bile ductular epithelium [21, 22], but the role of induced changes in biliary [Ca2+]i s still unclear. For example, UDCA and its conjugates were poor calcium binding agents, the free ionized [Ca"] in bile would remain high, thereby risking calcium salt precipitation
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