Plasma lipoproteins cholesterol esters, metabolic role

Abnormal lipoproteins are produced under various metabolic conditions. P-VLDL, a triglyceride-depleted, cholesterol-enriched form of VLDL, accumulates in the plasma of cholesterol-fed animals [13,14] or of humans with type III hyperlipoproteinemia [15]. In patients with this disease, the accumulation of j8-VLDL is believed to be due to incomplete clearance of chylomicron remnants by the liver. Slow turnover of remnants allows them to accumulate cholesteryl esters and thus to evolve into j8-VLDL particles [16,17]. -VLDL (density <1.006 g/ml, j8-electro-phoretic mobility) contain both apo-B and apo-E and may play a significant role in the formation of atherosclerotic foam cells [18]. 

Lipoproteins are macromolecular assemblies that contain proteins and lipids, including free and esterified cholesterol, triglycerides, and phospholipids. The protein components, known as apoUpoprotems, provide structural stability to the lipoproteins, and also may function as ligands in hpoprotein-receptor interactions or as cofactors in enzymatic processes that regulate lipoprotein metabolism. In aU Upoprotems, the most water-insoluble lipids (cholesteryl esters and triglycerides) are core components, and the more polar, water-soluble components (apoproteins, phospholipids, and unesterified cholesterol) are located on the surface. The major classes of lipoproteins and their properties are presented in Table 35-1. Table 35-2 describes apoproteins that have well-defined roles in plasma lipoprotein metabolism. 

An inherited lack of, or deficiency in, cell surface receptors for low density lipoproteins results in a condition, familial hypercholesterolaemia, in which blood cholesterol concentrations are rather high. This condition, if untreated, leads to severe vascular disease and death from ischaemic heart disease. Lipids are involved in several ways. First, one of the characteristics of developing atherosclerotic plaques is an accumulation of lipids, particularly cholesteryl esters, which are derived from plasma lipoproteins secondly, lipids are involved (because of their role as precursors of eicosanoids) in the formation of thrombi which may block arteries and cause ischaemia. Another risk factor for ischaemic heart disease that involves lipid metabolism is obesity, characterized by an excessive accumulation of adipose tissue. In particular, upper body obesity is also associated with Type II diabetes and hyperinsulinaemia. Hyperlipoproteinaemia is secondary to obesity and diabetes mellitus and if these conditions are treated, blood lipid concentrations return to normal. 

Lecithin-cholesterol acyltransferase is a water-soluble plasma enzyme that plays an important role in the metabolism of HDLs by catalyzing the formation of cholesteryl esters on HDLs through the transfer of fatty acids from the sn-2 position of phosphatidylcholine to cholesterol (Jonas, 1986). ApoA-1 is the major cofactor of LCAT in HDLs and reconstituted lipoproteins (Fielding et ai, 1972). Many laboratories have used techniques such as synthetic peptide analogs (Anantharamaiah et ai, 1990a Anantharamaiah, 1986), monoclonal antibodies (Banka et al., 1990), and recombinant HDL particles (Jonas and Kranovich, 1978) to attempt to identify the major LCAT-activating region of apoA-I. 

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