Lipid-protein complexes as cholesterol pronucleating agents in human bile.

Abstract Among the various substances which accelerate the formation of cholesterol crystals in cholesterol supersaturated bile are proteins obtained from the bile by affinity chromatography on con A-Sepharose. Several such con A binding proteins have been identified and shown to mediate acceleration of cholesterol crystal formation in vitro . However, the major protein fraction, which does not bind con A, has been studied rarely. Investigation of the effect of this latter bile protein fraction on cholesterol crystallization is the aim of this study. Contrary to results published to date, the con A nonbinding protein fraction exerted a higher cholesterol crystallization promoting activity than the con A binding fraction. Delipidation as well as proteolytic degradation sharply decreased the activity of both fractions. Albumin was identified as the main component of the con A nonbinding fraction. A lipid–protein complex formed from the lipid and albumin possessed a very high cholesterol crystallization promoting activity whereas albumin or the lipid alone showed much lower activity. Bivalent ions, especially Mn 2+ and Ca 2+ , increased the promoting activity of the lipid–protein complex. Thus, albumin and other bile proteins can bind noncovalently biliary lipid material and such lipid–protein complexes may act as the main cholesterol crystallization promoter in the human bile.