The hydrophobic-hydrophilic balance of bile salts. Inverse correlation between reverse-phase high performance liquid chromatographic mobilities and micellar cholesterol-solubilizing capacities.
The hydrophobic-hydrophilic balance of bile salts. Inverse correlation between reverse-phase high performance liquid chromatographic mobilities and micellar cholesterol-solubilizing capacities.
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发表时间：
1982
影响因子：
6.5
通讯作者：
M. Armstrong;M. Carey
中科院分区：
文献类型：
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作者：
M. Armstrong;M. Carey
为了定量研究胆盐的疏水-亲水特性，我们测定了单体胆盐溶液的反相高效液相色谱（HPLC）迁移率和100 mM胶束溶液的平衡胆固醇增溶能力。对普通胆汁盐（熊去氧胆酸盐、UDC、胆酸盐、C、鹅去氧胆酸盐、CDC和脱氧胆酸盐、DC）的研究表明，与亲水性相关的HPLC迁移率除受羟基官能团数量影响外，还受羟基官能团位置和方向的显著影响，迁移率按UDC > C > CDC > DC的顺序降低。胆汁盐的结合也很重要，因为牛磺酸（T）-结合物的HPLC迁移率大于甘氨酸（G）-结合物，甘氨酸（G）-结合物又大于游离胆汁盐。平衡胶束胆固醇溶解度也受到胆汁盐结构的影响，并与亲水性成反比，溶解度按DC > CDC > C > UDC与游离胆汁盐> G-缀合物> T缀合物的顺序降低。对于每个胆汁盐系列，以摩尔分数单位表示的胆固醇增溶能力与HPLC保留因子（k '）的双对数图给出了线性关系。线性回归方程被用来预测平衡胆固醇增溶能力的一些较不常见的胆汁盐从他们的HPLC保留因子。每个理论值都与完全由实验得出的值非常接近。比较较不常见胆汁盐与较常见胆汁盐的HPLC迁移率发现，不仅硫酸根和氧代取代基比α-羟基官能团更亲水，而且在二羟基物质中，单一赤道羟基官能团（如UDC中）（3 α，7 β）和在猪脱氧胆酸盐（3 α，6 α）中的亲水性比在3、7和/或12 α（轴向）位置处的两个或三个羟基官能团更高。这些研究共同表明，反相HPLC迁移率和平衡胆固醇增溶能力是彼此的反函数，并与胆汁盐分子的亲水性密切相关。此外，这里推导出的证据进一步加强了我们最近基于对许多其他物理化学性质的评估的推断（Carey，M。C.的方法，J-C Montet，M. C.菲利普斯，M. J. Armstrong和N. A.马泽，1981年。生物化学。20：3637-3648.）胆固醇可以通过与胆盐胶束的外（“亲水”）表面的疏水和亲水缔合而不是与胶束内部的疏水表面的疏水缔合而溶解在胶束胆盐溶液中。阿姆斯特朗，M。J.，和M. C.凯里胆汁盐的疏水-亲水平衡。反相高效液相色谱迁移率与胶束增溶胆固醇能力的负相关性。
To examine quantitatively the hydrophobic-hydrophilic properties of bile salts, we determined the reverse-phase high performance liquid chromatographic (HPLC) mobilities of monomeric bile salt solutions and the equilibrium cholesterol-solubilizing capacities of 100 mM micellar solutions. Studies with the common bile salts (ursodeoxycholate, UDC, cholate, C, chenodeoxycholate, CDC, and deoxycholate, DC) demonstrated that HPLC mobility, which correlates with hydrophilicity, was markedly influenced by both position and orientation, in addition to number, of hydroxyl functions, in that mobility decreased in the order UDC > C > CDC > DC. Conjugation of the bile salt was also important, in that the HPLC mobility of the taurine (T)-conjugates was greater than the glycine (G)-conjugates which in turn was greater than that of the free bile salts. Equilibrium micellar cholesterol solubilities were also influenced by bile salt structure and correlated inversely with hydrophilicity, in that solubility decreased in the order DC > CDC > C > UDC with free bile salts > G-conjugates > T conjugates. For each bile salt series, double logarithmic plots of the cholesterol-solubilizing capacities expressed in mole fraction units versus the HPLC retention factors (k') gave linear relationships. Linear regression equations were employed to predict the equilibrium cholesterol-solubilizing capacities of a number of less common bile salts from their HPLC retention factors. Each theoretical value agreed closely with that derived entirely by experiment. A comparison of the HPLC mobilities of the less common bile salts with the more common species revealed that not only were sulfate and oxo substituents more hydrophilic than alpha-oriented hydroxyl functions, but, in the dihydroxy species, a single equatorial hydroxyl function such as in UDC (3alpha,7beta) and in hyodeoxycholate (3alpha,6alpha) was more hydrophilic than two or three hydroxyl functions at 3, 7, and/or 12alpha (axial) positions. These studies taken together suggest that reverse-phase HPLC mobility and equilibrium cholesterol-solubilizing capacities are inverse functions of each other and correlate closely with the hydrophilicity of bile salt molecules. In addition, the evidence here deduced further strengthens our recent deductions based on an evaluation of a number of other physical-chemical properties (Carey, M. C., J-C. Montet, M. C. Phillips, M. J. Armstrong, and N. A. Mazer, 1981. Biochemistry. 20: 3637-3648.) that cholesterol may be solubilized in micellar bile salt solutions by both hydrophobic and hydrophilic association with the external ("hydrophilic") surface of bile salt micelles rather than with the hydrophobic surface of the micelle's interior.-Armstrong, M. J., and M. C. Carey. The hydrophobic-hydrophilic balance of bile salts. Inverse correlation between reverse-phase high performance liquid chromatographic mobilities and micellar cholesterol-solubilizing capacities.