Acyl chain unsaturation modulates distribution of lecithin molecular species between mixed micelles and vesicles in model bile. Implications for particle structure and metastable cholesterol solubilities.

De Cohen,Mc Carey

doi:10.1016/s0022-2275(20)41959-5

Abstract

We determined the distribution of lecithin molecular species between vesicles and mixed micelles in cholesterol super-saturated model biles (molar taurocholate-lecithin-cholesterol ratio 67:23:10, 3 g/dl, 0.15 M NaCl, pH approximately 6-7) that contained equimolar synthetic lecithin mixtures or egg yolk or soybean lecithins. After apparent equilibration (48 h), biles were fractionated by Superose 6 gel filtration chromatography at 20 degrees C, and lecithin molecular species in the vesicle and mixed micellar fractions were quantified as benzoyl diacylglycerides by high performance liquid chromatography. With binary lecithin mixtures, vesicles were enriched with lecithins containing the most saturated sn-1 or sn-2 chains by as much as 2.4-fold whereas mixed micelles were enriched in the more unsaturated lecithins. Vesicles isolated from model biles composed of egg yolk (primarily sn-1 16:0 and 18:0 acyl chains) or soy bean (mixed saturated and unsaturated sn-1 acyl chains) lecithins were selectively enriched (6.5-76%) in lecithins with saturated sn-1 acyl chains whereas mixed micelles were enriched with lecithins composed of either sn-1 18:1, 18:2, and 18:3 unsaturated or sn-2 20:4, 22:4, and 22:6 polyunsaturated chains. Gel filtration, lipid analysis, and quasielastic light scattering revealed that apparent micellar cholesterol solubilities and metastable vesicle cholesterol/lecithin molar ratios were as much as 60% and 100% higher, respectively, in biles composed of unsaturated lecithins. Acyl chain packing constraints imposed by distinctly different particle geometries most likely explain the asymmetric distribution of lecithin molecular species between vesicles and mixed micelles in model bile as well as the variations in apparent micellar cholesterol solubilities and vesicle cholesterol/lecithin molar ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

Highlights

We determined the distribution of lecithin molecular species between vesicles and mixed micelles in cholesterol supersaturated model biles that contained equimolar synthetic lecithin mixtures or egg yolk or soybean lecithins
Kinetics of bile salt-vesicle interactions were most rapid with unsaturated lecithin-rich vesicles [13], suggesting that lecithin molecular species may strongly modulate physical-chemical interactions among bile salts and other biliary lipids
As in our published work, we demonstrated that Superose 6 gel filtration of a typical model bile used in this study using an intermicellar-intervesicular concentration of 7.5 mM taurocholate as eluant, yielded vesicles

Summary

Introduction

We determined the distribution of lecithin molecular species between vesicles and mixed micelles in cholesterol supersaturated model biles (molar taurocholate-lecithin-cholesterol ratio 67:23:10, 3 g/dl, 0.15 M NaCI, p H -6-7) that contained equimolar synthetic lecithin mixtures or egg yolk or soybean lecithins. Lipid analysis, and quasielastic light scattering revealed that apparent micellar cholesterol solubilities and metastable vesicle cholesterol/lecithin molar ratios were as much as 60% and 100% higher, respectively, in biles composed of unsaturated lecithins. Acyl chain packing constraints imposed by distinctly different particle geometries most likely explain the asymmetric distribution of lecithin molecular species between vesicles and mixed micelles in model bile as well as the variations in apparent micellar cholesterol solubilities and vesicle cholesterolflecithin molar ratios. Acyl chain unsaturation modulates distribution of lecithin molecular species between mixed micelles and vesicles in model bile. Recent studies from our laboratory [12,13,14] have suggested that, during early bile formation, bile salts structurally alter lecithin-rich vesicles in a step-wise series of physical-chemical interactions that result in the dispersion of secreted biliary lipids as mixed micelles or mixed micelles plus cholesterol-rich vesicles.

Methods

Results

Conclusion