Roles of LCAT and Lipid Transfer Protein in HDL Metabolism

Abstract

The metabolism of HDL is central to plasma cholesterol transport. In the postabsorptive state cholesterol enters the plasma mainly as free cholesterol, either as a constituent of lipoproteins secreted by the liver or intestine or by diffusion from tissues down a concentration gradient maintained by the esterification of cholesterol within the plasma. This esterification is catalyzed by LCAT which interacts preferentially with HDL (Fielding and Fielding 1971). Most of the newly formed cholesteryl esters are initially incorporated into HDL (Rajaram and Barter 1985). The esterification also maintains a concentration gradient between the different plasma lipoprotein fractions, ensuring that free cholesterol in lipoproteins secreted from the liver and intestine is also channelled into HDL. Thus, regardless of its origin, a major proportion of the cholesterol entering plasma is converted into cholesteryl esters and incorporated into the core of HDL. Subsequent activity of the lipid transfer protein (LTP) then promotes a redistribution of cholesteryl esters from HDL to other plasma lipoprotein fractions. These transfers represent the major pathway by which cholesteryl esters become incorporated into the VLDL and LDL in human plasma (Rajaram and Barter 1985). Given that VLDL are catabolized to LDL in vivo, the end result of the transfer process is a delivery of cholesteryl esters to the LDL fraction and thus a regulated uptake by whatever tissues possess the appropriate receptors.