High density lipoprotein receptors

FIGURE 3.2.2 Metabolic pathways of carotenoids such as p-carotene. CM = chylomicrons. VLDL = very low-density lipoproteins. LDL = low-density lipoproteins. HDL = high-density lipoproteins. BCO = p-carotene 15,15 -oxygenase. BCO2 = p-carotene 9, 10 -oxygenase. LPL = lipoprotein lipase. RBP = retinol binding protein. SR-BI = scavenger receptor class B, type I. 

Fig. 1. Simplified schematic summary of the essential pathways for receptor-mediated human lipoprotein metabolism. The liver is the crossing point between the exogenous pathway (left-hand side), which deals with dietary lipids, and the endogenous pathway (right-hand side) that starts with the hepatic synthesis of VLDL. The endogenous metabolic branch starts with the production of chylomicrons (CM) in the intestine, which are converted to chylomicron remnants (CMR). Very-low-density lipoprotein particles (VLDL) are lipolyzed to LDL particles, which bind to the LDL receptor. IDL, intermediate-density lipoproteins LDL, low-density lipoproteins HDL, high-density lipoproteins LCAT, lecithinxholesterol acyltransferase CETP, cholesteryl ester transfer protein A, LDL receptor-related protein (LRPl) and W, LDL receptor. Lipolysis denotes lipoprotein lipase-catalyzed triacylglycerol lipolysis in the capillary bed.

Scheme 113.1 Schematic overview of cholesterol metabolism and main proposed mechanisms of action of phytosterols. 1. The absorption of dietary and/or biliary cholesterol is reduced by competition with PS for incorporation into mixed micelles. 2. Esterification of free cholesterol in the enterocyte is reduced by competition with PS for ACAT-2 enzyme. 3. Upregulation of the heterodimer ABCG5/G8 by PS can increase intestinal and hepato-biliar secretion. 4. Upregulation of ABCAl by PS can increase the incorporation of sterols into nascent HDL. 5. Increased cholesterol excretion via TICE. 6. Although it is not directly mediated by PS, the lower levels of hepatic cholesterol can lead to a lower VLDL secretion and upregulation of LDL receptor, which improves the clearance of plasma cholesterol. Abbreviations FC free cholesterol, CE cholesterol esters, ACAT-2 Acyl-CoA cholesterol O-acyltransferase 2, CM chylomicron, CMR chylomicron remnant, TICE transintestinal cholesterol efflux, LDL low-density lipoprotein, IDL intermediate-density lipoprotein, HDL high-density lipoprotein...

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...

Heparin Sulfate Proteoglycans Hepatic Lipase Hepatitis Hepatitis C Heptahelical Domain Heptahelical Receptors HERG-channels Heterologous Desensitization Heterologous Expression System Heterotrimeric G-Proteins Hidden Markov Model High-density Lipoprotein (HDL)... 

Figure 25-3. Metabolic fate of chylomicrons. (A, apolipoprotein A B-48, apolipoprotein B-48 , apolipoprotein C E, apolipoprotein E HDL, high-density lipoprotein TG, triacylgiycerol C, cholesterol and cholesteryl ester P, phospholipid HL, hepatic lipase LRP, LDL receptor-reiated protein.) Only the predominant lipids are shown.

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

Figure 26-6. Transport of cholesterol between the tissues in humans. (C, unesterified choiesterol CE, cho-iesteryi ester TG, triacyigiyceroi VLDL, very iow density iipoprotein iDL, intermediate-density iipoprotein LDL, iow-density iipoprotein HDL, high-density iipoprotein ACAT, acyi-CoA choiesteroi acyitransferase LCAT, iecithinxhoiesteroi acyitransferase A-i, apoiipoprotein A-i CETP, choiesteryi ester transfer protein LPL, lipoprotein iipase HL, hepatic iipase LRP, LDL receptor-reiated protein.)...

Lipoproteins. A lipoprotein is an endogenous macromolecule consisting of an inner apolar core of cholesteryl esters and triglycerides surrounded by a monolayer of phospholipid embedded with cholesterol and apoproteins. The functions of lipoproteins are to transport lipids and to mediate lipid metabolism. There are four main types of lipoproteins (classified based on their flotation rates in salt solutions) chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). These differ in size, molecular weight, and density and have different lipid, protein, and apoprotein compositions (Table 11). The apoproteins are important determinants in the metabolism of lipoproteins—they serve as ligands for lipoprotein receptors and as mediators in lipoproteins interconversion by enzymes. 

Acton, S, Rigotti, A, Landschulz, KT, Xu, S, Hobbs, HH, and Krieger, M, 1996. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 271, 518-520. 

Ji, Y, Jian, B, Wang, N, Sun, Y, Moya, ML, Phillips, MC, Rothblat, GH, Swaney, JB, and Tall, AR, 1997. Scavenger receptor BI promotes high density lipoprotein-mediated cellular cholesterol efflux. J Biol Chem 272, 20982-20985. 

Krieger, M, 1999. Charting the fate of the good cholesterol Identification and characterization of the high-density lipoprotein receptor SR-BI. Annu Rev Biochem 68, 523-558. 

Lorenzi, I, von Eckardstein, A, Cavelier, C, Radosavljevic, S, and Rohrer, L, 2008. Apolipoprotein A-I but not high-density lipoproteins are internalised by RAW macrophages Roles of ATP-binding cassette transporter A1 and scavenger receptor BI. JMolMed 86, 171-183. 

Tserentsoodol, N, Gordiyenko, NV, Pascual, I, Lee, JW, Fliesler, SJ, and Rodriguez, IR, 2006a. Intraretinal lipid transport is dependent on high density lipoprotein-like particles and class B scavenger receptors. 

Webb, NR, Connell, PM, Graf, GA, Smart, EJ, de Villiers, WJ, de Beer, FC, and van der Westhuyzen, DR, 1998. SR-BII, an isoform of the scavenger receptor BI containing an alternate cytoplasmic tail, mediates lipid transfer between high density lipoprotein and cells. J Biol Chem 273, 15241-15248. 

CD36 Cluster of differentiation 36, a receptor for high-density lipoprotein... 

X.-A. Li, W. B. Titlow, B. A. Jackson, N. Giltiay, M. Nikolova-Karakashian, A. Uittenbogaard, and E. J. Smart. High Density Lipoprotein Binding to Scavenger Receptor, Class B, Type I Activates Endothelial Nitric-oxide Synthase in a Ceramide-dependent Manner. J. Biol. Chem. 277 11058-11063 (2002). 

Cholesterol is carried in the bloodstream by hpoproteins such as low density lipoprotein (LDL, or bad cholesterol ) and high density lipoprotein (HDL, good cholesterol ). LDL carries cholesterol from the liver to other parts of the body. LDL attaches to receptors (see Chapter 2) on the cell surface and is taken into the cell interior. It is then degraded and the cholesterol is used as a component for the cell membrane. When there is excessive cholesterol inside the cell, it leads to a reduction in the synthesis of LDL receptors. 

Figure 22.10 Reverse cholesterol transfer. High density lipoprotein (HDL) collects cholesterol from cells in various tissues/ organs the complex is then transported in the blood to the liver where it binds to a receptor on the hepatocyte, is internalised and the cholesterolis released into the hepatocyte. This increases the concentration in the liver cells which then decreases the synthesis of cholesterol by inhibition of the rate-limiting enzyme in cholesterol synthesis, HMG-CoA synthase. The cholesterol is also secreted into the bile or converted to bile acids which are also secreted into the bile, some of which is lost in the faeces (Chapter A).

Lipoproteins are classified into five groups. In order of decreasing size and increasing density, these are chylomicrons, VLDLs (very-low-density lipoproteins), IDLs (inter-mediate-density lipoproteins), LDLs (low-density lipoproteins), and HDLs (high-density lipoproteins). The proportions of apoproteins range from 1 % in chylomicrons to over 50% in HDLs. These proteins serve less for solubility purposes, but rather function as recognition molecules for the membrane receptors and enzymes that are involved in lipid exchange. 

---