Molecular species composition of inter-mixed micellar/vesicular bile salt concentrations in model bile: dependence upon hydrophilic-hydrophobic balance

Abstract

We systematically studied the bile salt (BS) species composition of the intermixed micellar/vesicular (non-lecithin-associated) BS concentrations (IMC) of model biles using physiological biliary compositions prepared with mixtures of 12 common BS of humans. BS distributions in the IMC, which was composed of monomers plus simple micelles, were determined by rapid centrifugal ultrafiltration and/or modified equilibrium dialysis as functions of total lipid concentration, BS/lecithin ratio, cholesterol content, pH, and the weighted hydrophobic index of BS species. IMC values increased from 3 to 9.5 mM with increases in total lipid concentration and BS/lecithin ratio, but decreased appreciably as the overall BS composition of physiological BS mixtures became more hydrophobic. However, IMC values were not altered by increases in cholesterol content (0-10%) that induced a phase transition from a one-phase micellar system to a two-phase system of micelles and vesicles. As pH values were decreased (8 to 5), with partial protonation but not precipitation of glycine-conjugated BS (pK'a approximately 4.3 by titration), IMC values decreased slightly. For all model biles studied, IMC values of BS mixtures were markedly smaller than those previously found for model biles composed with taurocholate (Donovan, J. M. et al. 1991. J. Lipid Res. 32: 1501-1512). Hydrophilic BS were preferentially distributed in the IMC, whereas hydrophobic BS were preferentially associated with lecithin in mixed micelles and vesicles. Hence, BS composition, in addition to total lipid composition and BS/lecithin ratio, is a critical determinant of the relative and absolute concentrations of the BS species in the inter-mixed micellar/vesicular bile salt concentration.