Calcium affinity for biliary lipid aggregates in model biles: complementary importance of bile salts and lecithin.
OBJECTIVE
Despite putative roles of calcium in biliary physiology and gallstone formation, quantitative aspects of calcium binding to bile salt (BS) monomers, simple micelles, mixed micelles, and vesicles, which constitute the lipid aggregates in bile, remain unexplored.


METHODS
Calcium activity was measured using the calcium electrode in pathophysiologically relevant model biles composed of either individual BS species or a physiological mixture of glycine and taurine conjugates, as functions of lecithin and cholesterol contents and total lipid concentration.


RESULTS
Calcium binding increased with increasing BS concentrations and lecithin contents and varied with species (dihydroxy > trihydroxy BS) and with conjugation (unconjugated > glycine conjugates > taurine conjugates). Although lecithin/cholesterol vesicles did not bind detectable calcium, when taurocholate was incorporated into membrane bilayers, calcium binding was substantially greater than with equimolar BS alone. Added cholesterol did not alter calcium binding, despite cholesterol saturation of biliary lipid aggregates and induction of liquid crystalline and solid crystalline-phase transitions.


CONCLUSIONS
In model biles, most calcium is bound to mixed micelles, with minor contributions by BS monomers, simple micelles, and vesicles. It is proposed that BS-induced binding of calcium to vesicles and mixed micelles may be important in nucleation of cholesterol and bilirubinates from native bile.
Donovan
J M
JM
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.
Leonard
M R
MR
Batta
A K
AK
Carey
M C
MC
D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000502:physiology*; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D004530:Egg Yolk / Q000378:metabolism; D050356:Lipid Metabolism; D008823:Micelles; D010713:Phosphatidylcholines / Q000378:metabolism / Q000494:pharmacology*; D013656:Taurocholic Acid / Q000378:metabolism
D001647:Bile Acids and Salts; D008823:Micelles; D010713:Phosphatidylcholines; D013656:Taurocholic Acid; D002784:Cholesterol; D002118:Calcium