Current concepts of the molecular structure and metabolism of human apolipoproteins and lipoproteins.

Abstract

During the last few years major advances have occurred in our knowledge of the structure, function, and metabolism of the plasma lipoproteins. Twelve human apolipoproteins have been isolated and characterized. The primary structure of apolipoproteins A-I, A-II, C-I, C-II, and C-III have been elucidated. The primary structure of these apolipoproteins contain no unique sequences, however the primary structure of several of the apolipoproteins contain segments which can be modeled into amphipathic helices. The helical segments may be important in protein-protein as well as protein-lipid interactions. The molecular properties of the apolipoproteins have been investigated and shown to undergo self-association with major increases in conformation. The molecular organization of the plasma lipoprotein particle has been studied, and an iceberg-sea model has been proposed. This model emphasizes the micellar organization of the phospholipids, and the possibility of secondary, tertiary as well as quaternary structure of the apolipoprotein associated with the lipoprotein particle. The metabolism of plasma lipoproteins has been extensively analyzed over the last several years. Two general types of apolipoprotein-lipoprotein particle interactions have been recognized. The first type involves a "quasi-irreversible" interaction between the apolipoprotein and lipoprotein particle, and is exemplified by apolipoprotein b. The second type of interaction is a "reversible" apolipoprotein-lipoprotein particle interaction. Apolipoproteins a-I, A-II, C-I, C-II, C-III, and E are examples of the reversible interaction. Within this framework two major apoB-lipoprotein particle cascades have been proposed. ApoB-triglyceride rich lipoproteins including chylomicrons and hepatic VLDL undergo sequential triglyceride hydrolysis. Following triglyceride hydrolysis chylomicrons are converted to remnants with hydrated densities principally of VLDL and IDL. Liver apoB-VLDL is converted initially to IDL and finally to LDL. Apolipoproteins which undergo reversible interactions are present in virtually all density fractions and the distribution of these apolipoproteins is determined by the laws of mass action. With these concepts rapid progress has been made in our understanding of apolipoprotein-lipoprotein biochemistry, physiology, and clinical disorders of lipoproteins and atherosclerosis. The next several years will undoubtedly provide further insights into the structure, function, and metabolism of plasma lipoproteins.