MOLECULAR-SPECIES COMPOSITION OF INTER-MIXED MICELLAR VESICULAR BILE-SALT CONCENTRATIONS IN MODEL BILE - DEPENDENCE UPON HYDROPHILIC-HYDROPHOBIC BALANCE/

We systematically studied the bile salt (BS) species composition of th e intermixed micellar/vesicular (non-lecithin-associated) BS concentra tions (IMC) of model biles using physiological biliary compositions pr epared with mixtures of 12 common BS of humans. BS distributions in th e IMC, which was composed of monomers plus simple micelles, were deter mined 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 sp ecies. IMC values increased from 3 to 9.5 mM with increases in total l ipid concentration and BS/lecithin ratio, but decreased appreciably as the overall BS composition of physiological BS mixtures became more h ydrophobic. However, IMC values were not altered by increases in chole sterol content (0-10%) that induced a phase transition from a one-phas e micellar system to a two-phase system of micelles and vesicles. As p H values were decreased (8 to 5), with partial protonation but not pre cipitation of glycine-conjugated BS (pK'a almost-equal-to 4.3 by titra tion), IMC values decreased slightly. For all model biles studied, IMC values of BS mixtures were markedly smaller than those previously fou nd for model biles composed with taurocholate (Donovan, J. M. et al. 1 991. J. Lipid Res. 32: 1501-1512). Hydrophilic BS were preferentially distributed in the IMC, whereas hydrophobic BS were preferentially ass ociated with lecithin in mixed micelles and vesicles. Hence, BS compos ition, in addition to total lipid composition and BS/lecithin ratio, i s a critical determinant of the relative and absolute concentrations o f the BS species in the inter-mixed micellar/vesicular bile salt conce ntration.