Inhibition of calcium phosphate precipitation by bile salts: a test of the Ca(2+)-buffering hypothesis.
The ability of bile salts to inhibit the precipitation of either calcium hydroxyapatite or its precursor, amorphous calcium phosphate, by reducing Ca2+ activity or poisoning nascent crystals was determined. When apatite precipitated rapidly (1-4 h), glycocholate and taurine-conjugated bile salts (up to 100 mM) had little effect on apatite formation, but prevented amorphous calcium phosphate precipitation by lowering Ca2+ activity. In contrast, glycodeoxycholate and glycochenodeoxycholate (2-3 mM) inhibited apatite formation for at least 24 h by poisoning embryonic apatite. When apatite precipitated slowly (> 24 h), all the dihydroxy bile salts prevented apatite formation for at least 4 days. At constant initial supersaturation, the phosphate concentration determined the degree of inhibition caused by the six bile salts mixed together in physiologic proportion. At low phosphate concentrations (1.2 mM) total inhibition was achieved by poisoning embryos (approximately -5 mM total bile salt), but with 4.0 mM phosphate only approximately 60% inhibition was attained (150 mM bile salt) by a combination of poisoning and Ca(2+)-buffering. Thus, at low supersaturation all dihydroxy bile salts can prevent apatite formation by reducing free Ca2+ (taurine and glycine conjugates) or poisoning embryos (glycine conjugates). With mixtures of bile salts at higher supersaturation, inhibition of apatite depends on a combination of poisoning and reduction of free Ca2+, mainly caused by glycodeoxycholate and glycochenodeoxycholate.
Crowther
R S
RS
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555.
Okido
M
M
D001647:Bile Acids and Salts / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis; D002130:Calcium Phosphates / Q000737:chemistry / Q000378:metabolism*; D017886:Durapatite / Q000737:chemistry / Q000378:metabolism*; D005999:Glycochenodeoxycholic Acid / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical
D001647:Bile Acids and Salts; D002130:Calcium Phosphates; C485828:alpha-tricalcium phosphate; C519480:amorphous calcium phosphate; C485830:tetracalcium phosphate; D005999:Glycochenodeoxycholic Acid; C485838:calcium phosphate, monobasic, anhydrous; D017886:Durapatite; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous; D002118:Calcium