Angell A H, Resnick M I
Division of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
J Urol. 1989 May;141(5):1255-8. doi: 10.1016/s0022-5347(17)41233-x.
Molecules and macromolecules are known to alter the process of crystallization, either through inhibition or promotion of nucleation, growth, and/or aggregation. One particular group of macromolecules, glycosaminoglycans (GAGs), has been of interest in our laboratory. The GAGs chondroitin A, chondroitin C, heparan sulfate, dermatan sulfate, hyaluronic acid, and keratan sulfate have all been shown to be inhibitors of calcium oxalate crystallization. Heparin, the only GAG which is not naturally present in urine, is the most potent inhibitor of all GAGs. Using the method of Langmuir isotherm adsorption, we studied the adsorption of certain GAGs onto calcium oxalate crystals. Under standardized conditions, heparin, chondroitin C, hyaluronic acid, and pentosan polysulfate (a synthetic polyanionic molecule similar to, but a weaker inhibitor than, heparin) were adsorbed onto calcium oxalate. The total amount of GAG required to maximally cover the crystal surface, as well as the equilibrium concentration at which surface was half-covered with GAG (inversely related to the desorption energy) were measured. Chondroitin C was adsorbed in the greatest amount, followed by heparin, pentosan polysulfate, and finally hyaluronic acid. Using the method of fiducial limits, the only insignificant difference was between heparin and chondroitin C, and between hyaluronic acid and pentosan polysulfate. Pentosan polysulfate required significantly higher equilibrium concentration than heparin and hyaluronic acid to cover half of the surface of the calcium oxalate crystals. The principle of Langmuir isotherm adsorption can be useful in predicting the effects of macromolecules on crystallization. Weaker inhibitors bind with less affinity than do stronger inhibitors. Further work is underway to characterize other inhibitors and promoters.
已知分子和大分子会改变结晶过程，其方式包括抑制或促进成核、生长和/或聚集。我们实验室对一类特殊的大分子——糖胺聚糖（GAGs）很感兴趣。已证实软骨素A、软骨素C、硫酸乙酰肝素、硫酸皮肤素、透明质酸和硫酸角质素这些糖胺聚糖都是草酸钙结晶的抑制剂。肝素是唯一一种天然不存在于尿液中的糖胺聚糖，是所有糖胺聚糖中最有效的抑制剂。我们采用朗缪尔等温吸附法研究了某些糖胺聚糖在草酸钙晶体上的吸附情况。在标准化条件下，将肝素、软骨素C、透明质酸和戊聚糖多硫酸盐（一种合成的聚阴离子分子，与肝素相似，但抑制作用较弱）吸附到草酸钙上。测定了最大程度覆盖晶体表面所需的糖胺聚糖总量，以及晶体表面被糖胺聚糖覆盖一半时的平衡浓度（与解吸能呈反比）。软骨素C的吸附量最大，其次是肝素、戊聚糖多硫酸盐，最后是透明质酸。采用置信限法，唯一无显著差异的是肝素与软骨素C之间，以及透明质酸与戊聚糖多硫酸盐之间。戊聚糖多硫酸盐覆盖草酸钙晶体表面一半所需的平衡浓度明显高于肝素和透明质酸。朗缪尔等温吸附原理可用于预测大分子对结晶的影响。较弱的抑制剂与晶体的结合亲和力低于较强的抑制剂。目前正在开展进一步的工作以鉴定其他抑制剂和促进剂。
