Qiu S M, Soloway R D, Crowther R S
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.
Hepatology. 1992 Nov;16(5):1280-9.
Of the major human bile salts, only the glycine-conjugated dihydroxy species prevent the transformation of amorphous calcium phosphate to calcium hydroxyapatite, a component of gallstones; we have proposed that this inhibition occurs by competition between the bile salt and HPO4(2-) anions for binding site on the apatite crystal embryo. Now we show that the binding affinity of bile salts to fully mature hydroxyapatite has the following order: glycine-conjugated dihydroxy salts > taurine-conjugated dihydroxy salts > glycocholate approximately taurocholate. Glycine-conjugated dihydroxy bile salts bound with high affinity as "premicellar" aggregates, but the remaining species appeared to bind as a wider range of aggregate sizes. Glycochenodeoxycholate binding was decreased as the pH increased from 6.6 to 9.8 and the apatite surface charge reversed from net positive to net negative. Binding was competitively inhibited by HPO4(2-), but not by H2PO4-. Ca2+ promoted the binding of glycochenodeoxycholate, taurochenodeoxycholate and glycocholate, and for the latter two bile salts the increase was associated with enhanced "premicellar" binding. The binding of taurocholate was not influenced by Ca2+. When either glycocholate or taurocholate was mixed with glycochenodeoxycholate, mixed aggregates were formed that had a lower affinity for apatite than had pure glycochenodeoxycholate aggregates. Because only glycine-conjugated dihydroxy bile salts inhibit apatite formation, these results suggest that inhibition depends on high-affinity "premicellar" bile salt-apatite binding.
在主要的人体胆汁盐中，只有甘氨酸结合的二羟基胆汁盐能阻止无定形磷酸钙转化为羟基磷灰石（胆结石的一种成分）；我们曾提出，这种抑制作用是通过胆汁盐和HPO4(2-)阴离子竞争磷灰石晶体胚胎上的结合位点而发生的。现在我们发现，胆汁盐与完全成熟的羟基磷灰石的结合亲和力顺序如下：甘氨酸结合的二羟基胆汁盐＞牛磺酸结合的二羟基胆汁盐＞甘氨胆酸盐≈牛磺胆酸盐。甘氨酸结合的二羟基胆汁盐以“前胶束”聚集体的形式高亲和力结合，但其余胆汁盐似乎以更广泛的聚集体大小范围结合。随着pH从6.6增加到9.8，磷灰石表面电荷从净正变为净负，甘氨鹅脱氧胆酸盐的结合减少。HPO4(2-)竞争性抑制结合，但H2PO4-无此作用。Ca2+促进甘氨鹅脱氧胆酸盐、牛磺鹅脱氧胆酸盐和甘氨胆酸盐的结合，对于后两种胆汁盐，结合增加与“前胶束”结合增强有关。牛磺胆酸盐的结合不受Ca2+影响。当甘氨胆酸盐或牛磺胆酸盐与甘氨鹅脱氧胆酸盐混合时，形成的混合聚集体对磷灰石的亲和力低于纯甘氨鹅脱氧胆酸盐聚集体。由于只有甘氨酸结合的二羟基胆汁盐抑制磷灰石形成，这些结果表明抑制作用取决于高亲和力的“前胶束”胆汁盐-磷灰石结合。
