Asymmetric distribution of phosphatidylcholine and sphingomyelin between micellar and vesicular phases: potential implications for canalicular bile formation

Both phosphatidylcholine (PC) and sphingomyelin (SM) are the major phosphol ipids in the outer leaflet of the hepatocyte canalicular membrane, Yet, the phospholipids secreted into bile consist principally (>95%) of PC. In orde r to understand the physical-chemical basis for preferential biliary PC sec retion, we compared interactions with bile salts (taurocholate) and cholest erol of egg yolk (EY)SM (mainly 16:0 acyl chains, similar to trace SM in bi le), buttermilk (BM)SM (mainly saturated long (>20 C-atoms) acyl chains, si milar to canalicular membrane SM) and egg yolk (EY)PC (mainly unsaturated a cyl chains at sn-2 position, similar to bile PC). Main gel to liquid-crysta lline transition temperatures were 33.6 degrees C for BMSM and 36.6 degrees C for EYSM. There were no significant effects of varying phospholipid spec ies on micellar sizes or intermixed-micellar/vesicular bile salt concentrat ions in taurocholate-phospholipid mixtures (3 g/dL, 37 degrees C, PL/BS + P L = 0.2 or 0.4). Various phases were separated from model systems containin g both EYPC and (EY or BM)SM, taurocholate, and variable amounts of cholest erol, by ultracentrifugation with ultrafiltration and dialysis of the super natant, At increasing cholesterol content, there was preferential distribut ion of lipids and enrichment with SM containing long saturated acyl chains in the detergent-insoluble pelletable fraction consisting of aggregated ves icles, In contrast, both micelles and small unilamellar resides in the supe rnatant it ere progressively enriched in PC. Although SM containing vesicle s without cholesterol were very sensitive to micellar solubilization upon t aurocholate addition, incorporation of the sterol rendered SM-containing ve sicles highly resistant against the detergent effects of the bile salt, The se findings may have important implications for canalicular bile formation.