Lipoprotein physiology

Abstract

Lipoproteins are spherical macromolecular complexes in which hydrophobic molecules of triglyceride and cholesteryl ester are enveloped within a monolayer of amphipathic molecules of phospholipids, free cholesterol, and apoproteins. The major lipoprotein classes include intestinally derived chylomicrons that transport dietary fats and cholesterol, hepatic-derived VLDL, IDL, and LDL that can be atherogenic, and hepatic- and intestinally derived HDL that are anti-atherogenic. Apoprotein B is necessary for the secretion of chylomicrons (apo B48) and VLDL, IDL, and LDL (apo B100). Post-translational regulation of the assembly of apo B-containing lipoproteins by core lipid availability seems to be the major mechanism for variations in secretion. Plasma levels of VLDL triglycerides are determined mainly by rates of secretion and LPL lipolytic activity; plasma levels of LDL cholesterol are determined mainly by the secretion of apo B100 into plasma, the efficacy with which VLDL are converted to LDL and by LDL receptor-mediated clearance. Regulation of HDL cholesterol levels is complex and is affected by rates of synthesis of its apoproteins, rates of esterification of free cholesterol to cholesteryl ester by LCAT, levels of triglyceride-rich lipoproteins and CETP-mediated transfer of cholesteryl esters from HDL, and clearance from plasma of HDL lipids and apoproteins. Normal lipoprotein transport is associated with low levels of triglycerides and LDL cholesterol and high levels of HDL cholesterol. When lipoprotein transport is abnormal, lipoproteins levels can change in ways that predispose individuals to atherosclerosis.