Human Biochemistry, Volume 1 - Murray R. 1993

Bioenergetics and Metabolism of Carbohydrates and Lipids
Transport and Storage of Lipids
Plasma Lipoprotein Metabolism - HDL Metabolism (Fig. 26.6)

The Liver and intestines synthesize and secrete HDL. However, newly formed HDL from the intestines contains only apolipoprotein A, lacking apolipoprotein C. The latter is synthesized in the liver and transferred to intestinal HDL upon entry into the bloodstream. HDL act as a reservoir for apolipoproteins C and E, which are essential for the METABOLISM of chylomicrons and VLDL.

Newly formed HDL consist of a disk-shaped phospholipid bilayer containing free Cholesterol and apoproteins. These Lipoproteins resemble particles found in the plasma of patients with a deficiency of the plasma enzyme lecithin-cholesterol acyltransferase (LCAT), as well as in patients with obstructive jaundice. LCAT, and potentially the LCAT activator apolipoprotein A-I, bind to HDL. LCAT catalyzes the reaction between surface Phospholipids and free cholesterol, yielding cholesterol esters and lysolecithin. Nonpolar cholesterol esters move into the internal Hydrophobic core of the bilayer, while lysolecithin is transferred to serum albumin. As the reaction proceeds, a nonpolar core is formed that expands the bilayer, resulting in a spherical pseudo-micellar HDL coated on the outside with a layer of Polar Lipids and apoproteins. Esterified cholesterol can be transferred from HDL to lower-density lipoproteins, such as chylomicrons, VLDL, and LDL, by cholesterol ester transfer protein (apolipoprotein D), which is another protein component of HDL. Cholesterol ester transfer protein D mediates The transport of cholesterol esters from HDL to liver Cells via chylomicron and VLDL remnants or LDL. Subsequently, the LCAT system ensures the removal of excess unesterified cholesterol from lipoproteins and Tissues. The liver, and possibly the intestine, serves as the site of ultimate degradation of HDL apoproteins.

To explain the transport of cholesterol from peripheral tissues to hepatic cells, a cycle of HDL transformations has been proposed (Fig. 26.6). This figure explains why the plasma concentration of HDL₂, on the one hand, and the concentrations of chylomicrons and VLDL vary reciprocally, while the concentration of HDL₂ simultaneously changes in proportion to lipoprotein lipase activity. The inverse correlation between the incidence of coronary atherosclerosis and HDL (HDL₂) concentration is likely because the latter reflects the efficiency of cholesterol removal from tissues. HDL_c has been detected in the Blood of animals in which hypercholesterolemia was induced by a specialized diet. This lipoprotein contains a large amount of cholesterol, with apolipoprotein E as its sole protein constituent. HDL_c is taken up by liver cells via apolipoprotein E receptors and LDL receptors. The latter are therefore sometimes referred to as apolipoprotein B-100, E receptors. Atherosclerotic plaques consist of phagocytes that have engulfed so much cholesterol that they have transformed into foam cells engorged with cholesterol esters. Most of these cells originate from macrophages that scavenge abnormal, cholesterol-rich lipoproteins, such as chemically modified LDL or β-VLDL (see p. 284). Research by Brown and Goldstein (1983) demonstrated that macrophages secrete both cholesterol (which binds to a suitable acceptor, such as HDL) and apolipoprotein E, which, following appropriate Processing involving LCAT, can serve as a source of cholesterol-rich HDL_c. Thus, HDL_c may play a crucial role in transporting cholesterol from various tissues to the liver (“reverse cholesterol transport”).

The data outlined above indicate that all plasma lipoproteins are interrelated and function as components of one or more metabolic cycles that drive the complex process of plasma lipid transport.