Lipoprotein receptors, binding affinity

Chappell, D.A. (1989) High receptor binding affinity of lipoproteins in atypical dysbetahpo-proteinemia (type III hyperlipoproteinemia). J. Clin. Invest., 84, 1906-1915. 

W9. Weisgraber, K. H., Innerarity, T. L., and Mahley, R. W., Role of lysine residues of plasma lipoproteins in high affinity binding to cell surface receptors on human fibroblasts. ]. Biol. Chem. 253, 9053-9062 (1978). 

The multireceptor binding ability of apoE bas important consequences in lipoprotein metabolism. Lipoprotein particles with one apoE per particle will compete on a more or less equal basis with LDL for LDL receptors and would be expected to be cleared at approximately equal rates. However, when the apoE content increases to four or more molecules per particle, the binding affinity increases dramatically through multireceptor interaction, with a corresponding increase in removal rate. 

LDL transports cholesterol to most extrahepatic parenchymal cells [121]. In contrast, the adrenal gland, ovary and testis utilise HDL cholesterol [122]. Studies in vitro show that LDL uptake is mediated by high-affinity receptor binding of the lipoprotein, subsequent endocytosis and catabolism [123]. However, other studies show that a significant portion of free cholesterol in serum lipoproteins can be transferred to the mycoplasma cell membrane by simple exchange [123,124]. A similar process may occur in eucaryotic cells [94]. 

The best-characterized lipoprotein receptor, the LDL receptor, specifically recognizes apoB-100 and apo E. Therefore, this receptor binds VLDL, IDL, and chylomicron remnants in addition to LDL. The binding reaction is characterized by its saturability and occurs with high affinity and a narrow range of specificity. Other receptors, such as the LDL receptor-related proteins (LRP) and the macrophage scavenger receptor (notably types SR-Al and SR-A2, which are located primarily near the endothelial surface of vascular endothelial cells), have broad specificity and bind many other ligands in addition to the blood lipoproteins. 

VLDLs, which have a density range of 0.95 to 1.006 g/ml, are produced in the liver and function as transporters for endogenons triglycerides and cholesterol to peripheral tissues. The primary apolipoprotein constitnents of VLDLs are apolipo-proteins B-lOO, Cs, and E. Apolipoprotein E present in VLDL plays an important role in plasma lipoprotein metabolism throngh its high binding affinity to cell surface EDL receptors, which could reduce plasma VLDL and LDL concentration as well as the atherosclerotic process. ... 

Anion exchange resins are basic polymers with a high affinity for anions. Because different anions compete for binding to them, they can be used to sequester anions. Clinically used anion exchange resins such as cholestyramine are used to sequester bile acids in the intestine, thereby preventing their reabsorption. As a consequence, the absorption of exogenous cholesterol is decreased. The accompanying increase in low density lipoprotein (LDL)-receptors leads to the removal of LDL from the blood and, thereby, to a reduction of LDL cholesterol. This effect underlies the use of cholestyramine in the treatment of hyperlipidaemia. 

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