Quantitative estimation of the hydrophilic-hydrophobic balance of mixed bile salt solutions.
Quantitative estimation of the hydrophilic-hydrophobic balance of mixed bile salt solutions.
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发表时间：
1989-05
影响因子：
6.5
通讯作者：
D. Heuman
中科院分区：
文献类型：
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作者：
D. Heuman
本文介绍了胆盐单体疏水性指数的推导，该指数定量地定义了胆盐混合物的复合亲水-疏水平衡。该指数基于用反相高效液相色谱法测定的胆盐容量因子的对数(固定相十八烷基硅烷；流动相甲醇-水70：30w/w，离子强度0.15)。将牛磺胆酸盐和牛磺胆酸石酸盐的指数分别设定为0和1已被随意标准化。牛磺熊去氧胆酸、牛磺酸猪去氧胆酸、牛磺酸鹅去氧胆酸和牛磺酸脱氧胆酸的指数分别为-0.47、-0.35、+0.46和+0.59。在pH 2.8~9.0范围内，牛磺酸偶联胆盐的容量因子和疏水指数恒定，而甘氨酸偶联胆盐和未偶联胆盐的亲水-疏水平衡受pH的影响较大。在碱性pH值大于8.5的条件下，完全电离的未结合胆盐(n=4)和甘氨酸结合胆盐(n=6)的疏水性指数分别与牛磺酸结合物相差0.14+/-0.02和0.05+/-0.01。在酸性pH<3.5时，4种非结合胆汁酸(质子化形式)的疏水性指数比相应盐(离子形式)的疏水性指数高0.76+/-0.04，而6种甘氨酸结合胆汁酸的疏水性指数仅比相应盐的疏水性指数高0.26+/-0.03。随着流动相离子强度的增加，盐型胆酸盐及其结合物的容量因子显著增加；质子化形式(胆酸和甘胆酸)的保留率仅受离子强度的影响很小。因此，胆汁酸和相应盐之间的亲水-疏水平衡的差异随着离子强度的增加而减小。给出了四种胆盐(完全电离)在完整肠肝循环条件下疏水性指数的计算实例。从疏水性最小到最疏水性的平均值是：大鼠(-0.31)比狗(0.11)小，仓鼠(0.22)比人(0.32)小。本研究为在较宽的pH范围内计算混合胆盐溶液的亲水-疏水平衡提供了合理的依据。
This paper describes the derivation of a bile salt monomeric hydrophobicity index that quantitatively defines the composite hydrophilic-hydrophobic balance of a mixture of bile salts. The index is based on the logarithms of bile salt capacity factors determined using reversed phase high performance liquid chromatography (HPLC) (stationary phase octadecyl silane; mobile phase methanol-water 70:30 w/w, ionic strength 0.15). It has been standardized arbitrarily to set indices of taurocholate and taurolithocholate to 0 and 1, respectively. Indices of tauroursodeoxycholate, taurohyodeoxycholate, taurochenodeoxycholate, and taurodeoxycholate were found to be -0.47, -0.35, +0.46, and +0.59, respectively. Whereas capacity factors and hydrophobicity indices of taurine-conjugated bile salts were constant for pH 2.8-9.0, the hydrophilic-hydrophobic balance of glycine-conjugated and unconjugated bile salts was strongly influenced by pH. At alkaline pH (greater than 8.5), hydrophobicity indices of fully ionized unconjugated (n = 4) and glycine-conjugated (n = 6) bile salts differed by only 0.14 +/- 0.02 and 0.05 +/- 0.01, respectively, from those of the corresponding taurine conjugates. At acid pH (less than 3.5) the hydrophobicity indices of four unconjugated bile acids (protonated form) exceeded those of the corresponding salts (ionized form) by 0.76 +/- 0.04; indices of six glycine-conjugated bile acids exceeded those of the corresponding salts by only 0.26 +/- 0.03. Capacity factors of the salt forms of cholate and its conjugates increased dramatically with increasing ionic strength of the mobile phase; retention of the protonated forms (cholic and glycocholic acids) was only minimally influenced by ionic strength. Thus the difference in hydrophilic-hydrophobic balance between a bile acid and its corresponding salt decreases with increasing ionic strength. Examples are given of calculation of hydrophobicity indices for biliary bile salts (fully ionized) from four species under conditions of intact enterohepatic circulation. Mean values, from least to most hydrophobic, were: rat (-0.31) less than dog (0.11) less than hamster (0.22) less than human (0.32). This study provides a rational basis for calculating the hydrophilic-hydrophobic balance of mixed bile salt solutions over a broad range of pH.