COLL 135

The physical chemistry of biliary lipids has been studied using a number of methods, including light scattering, small angle neutron scattering, and cryoelectron microscopy, under different physiological manipulation. Biliary lipid molecules are transported by specific transporters regulated by genes. Bile salts are transported as monomers, while cholesterol and phospholipids bud off as unilamellar vesicles from microdmains located at the outter leaflet of the liver cell lipid bilayer. After secretion, these molecules undergo a process of dynamic interconversion, depending on the concentration of bile. Bile salts self associate into simple micelles, which at low concentration, appear as rod shape structures. They then evolve into disc-like simple micelles which then incorporate cholesterol and phospholpids from the unilamellar vesicles into spherical mixed micelles. Mixed micelles coexist, at a given time, with bile salt monomers, simple micelles, and cholesterol-phospholipid vesicles. Under permitting conditions, vesicles can aggregate, fuse, and from which cholesterol can nucleate to form a microcrystal. This phase transition can be modified by proteins in the bile, either secreted by the liver, or by the gallbladder. Protein-lipid interactions, together with the magnitude of cholesterol saturation, constiute the major factors determining cholesterol precipitation and gallstone disease.

The single most important determimant of how the body disposes of excessive cholesterol is through the hepatic conversion to bile salts and its cosecretion with cholesterol into bile. A better understanding of the physical chemical regulation of biliary lipid microstructure holds the key to the secret of the treatment and prevention gallstone disease, cholestasis, and hypercholesterolemic disorders including cardiovascular disease, renal failure and strokes.