van Erpecum K J, Carey M C
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Biochim Biophys Acta. 1997 Apr 21;1345(3):269-82. doi: 10.1016/s0005-2760(97)00002-7.
Bile salts enhance secretion of cholesterol into bile and its subsequent solubilization with phosphatidylcholine in mixed micelles. Sphingomyelin, a major structural lipid of the hepatocyte canalicular membrane, and disaturated phosphatidylcholines are known to impede nucleation of solid cholesterol crystals in supersaturated model systems. To understand these effects physico-chemically, we compared the influence of bile salts on interactions of cholesterol with natural sphingomyelins, as well as with dipalmitoyl and egg yolk phosphatidylcholines using various in vitro systems. Submicellar bile salts enhanced significantly bidirectional transfer of dehydroergosterol (a fluorescent cholesterol analog) between sphingomyelin and egg yolk phosphatidylcholine vesicles in the rank order taurocholate < tauroursodeoxycholate < taurodeoxycholate. Quasielastic light scattering of serially diluted sphingomyelin-taurocholate mixtures (1:1 molar ratio, 3 g/dl) revealed metastable temperature-dependent transitions between globular micelles, rod-shaped micelles and vesicles, suggesting that phase transitions under these experimental conditions were metastable only at temperatures below 37 degrees C. Ternary phase diagrams of all sphingomyelins and dipalmitoyl phosphatidylcholine with cholesterol and taurocholate (37 degrees C, 3 g/dl, 0.15 M NaCl) were identical. Compared to systems containing egg yolk phosphatidylcholine, the 1-phase micellar zone and 2- and 3-phase solid cholesterol crystal-containing zones were reduced markedly while the 2-phase zone with stable cholesterol-sphingomyelin liquid crystals was greatly expanded. Our results suggest that the high affinity of cholesterol for sphingomyelin is lost in the presence of bile salts. Our findings may be relevant to secretion of cholesterol into bile and to its inability to crystallize in the hepatocyte canalicular lumen or its surrounding membranes.
胆盐可促进胆固醇分泌入胆汁，并随后在混合微团中与磷脂酰胆碱一起溶解。鞘磷脂是肝细胞膜小管膜的主要结构脂质，已知二饱和磷脂酰胆碱会阻碍过饱和模型系统中固体胆固醇晶体的成核。为了从物理化学角度理解这些作用，我们使用各种体外系统比较了胆盐对胆固醇与天然鞘磷脂以及二棕榈酰磷脂酰胆碱和蛋黄磷脂酰胆碱相互作用的影响。亚微摩尔浓度的胆盐显著增强了脱氢麦角固醇（一种荧光胆固醇类似物）在鞘磷脂和蛋黄磷脂酰胆碱囊泡之间的双向转移，其顺序为牛磺胆酸盐<牛磺熊去氧胆酸盐<牛磺脱氧胆酸盐。对系列稀释的鞘磷脂-牛磺胆酸盐混合物（摩尔比1:1，3 g/dl）进行的准弹性光散射显示，在球状微团、棒状微团和囊泡之间存在亚稳的温度依赖性转变，这表明在这些实验条件下，相变仅在低于37摄氏度的温度下才是亚稳的。所有鞘磷脂、二棕榈酰磷脂酰胆碱与胆固醇和牛磺胆酸盐（37摄氏度，3 g/dl，0.15 M氯化钠）的三元相图是相同的。与含有蛋黄磷脂酰胆碱的系统相比，单相微团区以及含二相和三相固体胆固醇晶体的区域显著减少，而含有稳定胆固醇-鞘磷脂液晶的二相区则大大扩展。我们的结果表明，在胆盐存在的情况下，胆固醇对鞘磷脂的高亲和力丧失。我们的发现可能与胆固醇分泌入胆汁以及其在肝细胞膜小管腔或其周围膜中无法结晶有关。
