Role of ABC transporters in secretion of cholesterol from liver into bile.

Abstract

By 1968, the basic principles underlying cholesterol solubility in bile had been established (1, 2). Free cholesterol (C) had been found to be almost entirely insoluble in water and very poorly soluble in bile salt solutions. Cholesterol was however very soluble in phosphotidylcholine (PC) lamellar liquid crystals (bilayers), and bile salts could solubilize the PC/C liquid crystal bilayers into mixed micelles, thus carrying the C into solution. In 1970, I speculated (3) that the molecular mechanism for biliary lipid secretion was “that bile salts penetrate the cannilicular membrane from the interior of the liver cell and dissect out specifically lecithin and cholesterol leaving the membrane protein and other structural lipids intact.” This hypothesis, based on the physical chemistry of the lipid systems, has now been proven to be almost entirely incorrect. It is now clear that all biliary lipids are secreted in a controlled way by ABC transporters, and that the physical chemistry of the lipid interactions probably occurs within the lumen of the canniliculus and biliary ducts.