The hydrophobic-hydrophilic balance of bile salts. Inverse correlation between reverse-phase high performance liquid chromatographic mobilities and micellar cholesterol-solubilizing capacities.
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.
D001647:Bile Acids and Salts / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002784:Cholesterol / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003102:Colloids; D008823:Micelles; D008956:Models, Chemical; D008958:Models, Molecular; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
D001647:Bile Acids and Salts; D003102:Colloids; D008823:Micelles; D002784:Cholesterol