Plasma cholesteryl ester transfer protein.

The plasma lipoproteins are continuously remodeled during their transit through the plasma compartment, owing to the action of lipid metabolizing enzymes and lipid transfer processes. These activities have a major effect on the composition, size, and concentration of the lipoproteins. Lipid transfer processes involving neutral lipids and phospholipids are mediated by specialized plasma proteins, called lipid transfer proteins. The plasma lipid transfer proteins include the cholesteryl ester transfer protein (CETP) with specificity for both neutral lipids and phospholipids, as well as a phospholipid transfer protein (PTP). The plasma lipid transfer proteins are analogous to the cellular lipid transfer proteins, which mediate the transfer of lipids between organelles (1) or from sites of intracellular synthesis into nascent lipoproteins (2). The importance of lipid transfer proteins in lipoprotein metabolism and cellular processes has recently been confirmed by the discovery of genetic deficiency states causing remarkable phenotypes (3-5). Lipid transfer particles, which mediate the movement of diglycerides between lipophorins, are also present in the hemolymph of insects (6). This review will focus on the plasma cholesteryl ester transfer protein. There have been several recent excellent reviews on plasma lipid transfer activities (7, 8). Since this topic was last reviewed in these pages (9), there has been considerable progress in understanding the biochemistry and properties of the plasma CETP. The CETP has been purified and cloned and the gene structure has been determined. The role of CETP in lipoprotein physiology has been illuminated by the availability of CETP neutralizing antibodies and the elucidation of human genetic CETP deficiency. CETP monoclonal antibodies have also been used to probe the structure-function relationships of CETP, although much remains to be learned in this area. Other areas for future investigation will include: I) the complex relationship of CETP to reverse cholesterol transport and atherogenesis; 2) the apparently pleiotropic functions of CETP in different cells and tissues, such as adipocytes, macrophages and lymphocytes; 3) the mechanisms of regulation of CETP gene expression by cholesterol and other factors; 4) the function of CETP-like genes in species without plasma CETP activity; and 5) the biochemical characterization and function of plasma phospholipid transfer proteins and CETP protein inhibitors.