On the solubility of calcium deoxycholate: kinetics of precipitation and the effect of conjugated bile salts and lecithin.
In view of the low solubility of calcium deoxycholate and the possible induction of cholesterol precipitation in the gallbladder by calcium insoluble salts, we find it of interest to study the precipitation of calcium deoxycholate and its dependence on other bile components. The findings of these studies were as follows: (i) Precipitation of calcium deoxycholate from mixtures of calcium chloride and monomeric deoxycholate (at concentrations below the critical micelle concentration (CMC] is very slow even at relatively high CaCl2 concentrations (more than 20 days at 50 mM CaCl2). (ii) At higher deoxycholic acid (DOC) concentrations, precipitation of micellar DOC is faster and requires much lower calcium chloride concentrations. For any given calcium concentration, the rate of precipitation is maximal at an optimal DOC concentration. In solutions containing 150 mM NaCl, the maximal rate of precipitation occurs at about 10 mM DOC, almost independent of Ca2+ concentration. At lower ionic strength (10 mM NaCl), the optimal DOC concentration is 30 mM. These observations suggest that the most important factors in determining the rate of Ca(DOC)2 precipitation are (a) the ratio between calcium ions bound to the surface of a DOC micelle, and the [DOC] (the Ca2+/DOC binding ratio) and (b) the concentration of DOC micelles. (iii) In the presence of conjugated deoxycholates, the crystallization of calcium deoxycholate is inhibited. Phosphatidylcholine has a similar, although smaller, inhibitory effect. Upon precipitation of calcium deoxycholate from a mixed micellar system containing sodium deoxycholate, phosphatidylcholine and cholesterol, the latter two components spontaneously form vesicles. The anti-nucleating effect of PC and conjugated bile salts is explained in terms of "poisoning" of the crystallization process. In view of the latter results we conclude that under normal conditions calcium deoxycholate is not likely to precipitate in the gallbladder.
Lichtenberg
D
D
Department of Physiology, Tel Aviv University, Ramat Aviv, Israel.
Younis
N
N
Bor
A
A
Kushnir
T
T
Shefi
M
M
Almog
S
S
Nir
S
S
D001647:Bile Acids and Salts / Q000378:metabolism*; D002118:Calcium / Q000032:analysis*; D011232:Chemical Precipitation; D002769:Cholelithiasis / Q000209:etiology; D003840:Deoxycholic Acid / Q000032:analysis*; D006801:Humans; D010713:Phosphatidylcholines / Q000378:metabolism*; D012995:Solubility
D001647:Bile Acids and Salts; D010713:Phosphatidylcholines; D003840:Deoxycholic Acid; D002118:Calcium