Lipid metabolism plasma concentrations, ApoE

The function of apoE in lipoprotein metabolism is reviewed in the sixth chapter by Karl Weisgraber. The three-dimensional structure of a 22-kDa fragment of human apoE (34.2 kDa) has been solved by X-ray crystallography the relation of this structure to the role of apoE in lipoprotein metabolism is discussed in detail, together with a critical and extensive examination of the chemistry and biology of this apolipoprotein which plays such a central role in lipoprotein metabolism. Apolipoprotein E has three major isoforms in the human population which affect lipoprotein metabolism differently, resulting in different levels of the plasma lipoproteins. The impact of structure on function and how plasma lipid concentrations are affected by the different apoE isoforms are the themes of this important chapter. 

LDL (diameter 200-250 A, density range 1.019-1.063 g/ml, /8-electrophoretic mobility, Fig. 1) are often termed )8-lipoproteins. LDL contain, by weight, 75% lipid (principally esterified cholesterol) and 25% protein which consists exclusively of apo-B (Fig. 2). LDL is the major vehicle for transport of cholesterol to peripheral tissues and normally accounts for about 70% of total plasma cholesterol [10]. LDL metabolism is of medical interest since there is a direct correlation between increased plasma LDL concentration and an increased incidence of atherosclerotic heart disease [11]. 

As far as HDL levels and metabolism are concerned, one result of the LCAT- and transfer protein-catalyzed reactions is the production of a dynamic spectrum of particles with a wide range of sizes and lipid compositions (Chapter 19). Nascent HDL particles contain mostly apo A1 and phospholipids, and undergo modulation and maturation in the circulation. For instance, the unesterified cholesterol incorporated into plasma HDL is converted to cholesteryl esters by LCAT, creating a concentration gradient of cholesterol between HDL and cell membranes, which is required for efficient cholesterol efflux from cells to HDL. In addition, cholesteryl ester transfer protein transfers a significant amount of HDL cholesteryl ester to VLDL, IDL, and LDL for further transport, primarily to the liver. Thus, a substantial fraction of cell-derived cholesterol is delivered as part of HDL indirectly to the liver via hepatic endocytic receptors for IDL and LDL this process is termed reverse cholesterol transport . However, receptor-mediated delivery of HDL cholesterol to cells is fundamentally different from the classic LDL receptor-mediated endocytic pathway, as described in Section 7.3.2. 

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