ApoB-100,E receptors

The WHHL model has stimulated major advances in our understanding of apoB receptors (G22). In particular, it has allowed a clear differentiation of two kinds of hepatic receptors one involved in the uptake of chylomicron remnants, recognizing (it is thought) apoE when in a particle containing apoB-48, and the other involved in the hepatic uptake of apoB-100-contain-ing VLDL, IDL, and LDL particles. The apoB-100 receptors, which also have an affinity for apoE and are referred to in this review as apoB-100, E receptors, are found in many extrahepatic cells. The WHHL rabbit is deficient in apoB-100, E receptors, but not in those receptors responsible for chylomicron clearance. 

ApoB-100,E receptors present in the liver of immature dogs and swine are suppressed by cholesterol feeding and are not apparently active in the liver of mature animals (H35, Mil). The hepatic apoB-100,E receptors are thought to be identical to the apoB-100 receptors demonstrated in many extrahepatic cell types (B21). ApoE-containing HDL in vitro have a 20- to 25-fold greater affinity for apoB-100, E receptors than LDL (16, P15) it seems, because there are four receptor binding sites for each molecule of HDLC as opposed to one binding site for LDL (P15, P16). 

In summary, it seems likely that, in the adult animal including man, apoE-containing HDL is taken up rapidly by the apoE receptors in the liver. Some apoE-containing HDL may also be taken up by apoB-100,E receptors in extrahepatic tissues. The significance of apoE-containing HDL in cholesterol metabolism in man is unknown, but this pathway may allow HDL cholesterol to be taken up by the liver. An apoE-enriched HDL fraction, larger than typical HDL but smaller than LDL, has been demonstrated in the plasma of normolipidemic subjects (G3). The cholesterol content of apoE-associated... 

It is likely that the major site of uptake of apoE-containing remnants of the triglyceride-rich lipoproteins is the liver. As apoC is removed and the apoE apoC ratio rises, so the remnant lipoprotein becomes more amenable to hepatic uptake by specific receptors (S25, S28, W16, W17). VLDL remnants and IDL also experience apoE-mediated binding by apoB,E receptors in hepatic cell membrane preparations (H35, Mil). The smallest apoE-rich VLDL subfractions from normolipidemic human plasma compete with LDL for fibroblast (apoB-100,E) receptors in vitro (T10) and in cultured fibroblasts (F17, G2, 17). ... 

The size of the VLDL particle in plasma diminishes and its density increases as triglyceride is hydrolyzed by endothelial lipoprotein lipase, and the particles are thus converted to intermediate-density lipoproteins (IDL) (B32, S35). The IDL detach from the endothelium, and some are taken up by hepatic B-100, E receptors. The remaining particles in the circulation are further depleted of some cholesteryl ester (by an unknown mechanism), and most of the remaining triglyceride (probably by hepatic triglyceride lipase, in the liver sinusoids) (D5). Hie resulting LDL particles are largely composed of cholesteryl ester as the core lipid and apoB-100 as the apolipoprotein. 

Manttari M, Koskinen P, Ehnholm C, Huttunen JK, Manninen V. Apolipo-protein E polymorphism influences the serum cholesterol response to dietary intervene blood is diminished due to mutations within the apoB-100 receptor binding domain [51]. A number of point mutations of the putativd its relation to E polymorphism. Orv Hetil 1994 135 735-741. 

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. 

Fig. 28.1. A schematic diagram depicting lipoprotein metabolism and the known genetic defects affecting lipoproteins. 28.1, Lipoprotein lipase (LPL) deficiency 28.2, apoC-II deficiency 28.3, apoE deficiency or mutations 28.4, hepatic lipase (HL) deficiency 28.5, LDL receptor deficiency or mutations 28.6, apoB-100 mutation in receptor binding region 28.7, apoA-I deficiency or mutations 28.7.3, ABCAl deficiency or mutations 28.8, LCAT deficiency 28.9, microsomal transfer protein (MTP) deficiency 28.10, apoB-100 synthesis or truncation mutations. Abbreviations C-II, apoC-II B, apoB E, apoE A-I, apoA-I VLDL, very-low-density lipoproteins IDL, intermediate-density lipoproteins LDL, low-density lipoproteins HDL, high-density lipoproteins LPL, lipoprotein lipase HL, hepatic lipase LCAT, lecithin cholesterol acyltransferase UC, unesterified cholesterol...

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