CETP, cholesteryl ester transfer protein

Figure 21-1 Movement of triacylglycerols from liver and intestine to body cells and lipid carriers of blood. VLDL very low density lipoprotein which contains triacylglycerols, phospholipids, cholesterol, and apolipoproteins B, and C. IDL intermediate density lipoproteins found in human plasma. LDL low density lipoproteins which have lost most of their triacylglycerols. ApoB-100, etc., are apolipoproteins listed in Table 21-2. LCAT, lecithin cholesterol acyltransferase CETP, cholesteryl ester transfer protein (see Chapter 22).

Figure 15-2. A simplified schematic of cholesterol transport. Cholesterol travels to non-hepatic cells, such as the macrophage, via VLDL and LDL particles, while excess cholesterol is shuttled to the liver via HDL particles. Note that AHCAl mediates nascent HDL formation by translocating cellular cholesterol and phospholipids to apolipoprotein A-I (apoA-I) in an active, energy-dependent reaction. CETP, cholesteryl ester transfer protein LCAT, lecithinxholesterol acyltransferase LDLR, low-density lipoprotein receptor SR-B1, scavenger receptor Bl.

Fig. 3. Metabolic interrelationships of lipoproteins (lipoprotein abbreviations are as given in Table I). LpL, Lipoprotein lipase LCAT, lecithin-cholesterol acyltransferase HL, hepatic lipase CETP, cholesteryl ester transfer protein. Solid lines represent interconversion of particles regular dashed lines represent movement of cholesterol irregular dashed lines represent transfer of lipids mediated by CETP.

Figure 26-21 Reverse cholesterol transport pathway. HDl High-density lipoproteins LDL, low-density lipoproteins tDL, intermediate-density lipoproteins HTL, hepatic lipoprotein lipase LCAT, lecithin cholesterol acyltransferase CETP, cholesteryl ester transfer protein apo E, apoiipoprotein E. Cholesterol is removed from macrophages and other arterial wall cells by an HDL-mediated process. The LCAT esterifies the cholesterol content of HDL to prevent it from reentering the ceils. Cholesterol esters are delivered to the liver by one of three pathways ( ) cholesterol esters are transferred from HDL to LDL by CETP and enter the liver through the specific LDL receptor pathway (2) cholesterol esters are selectively taken from HDL by HDL receptors and HDL particles are returned to circulation for further transport or (3) HDL have accumulated apo E and therefore the particles can enter the liver through remnant receptors, (From Gwynne JT. High density lipoprotein cholesterol levels as a marker of reverse cho/estero/ tronsport./ m j Cardiol I989 64 10G-I7G. Copyright 1989, with permission from Excerpta Medico Inc.)...

FIGURE 21-2. Overview of lipoprotein metabolism. (ACAT = acyl CoAxholesterol acyltransferase CETP = cholesteryl ester transfer protein FA = fatty acid FFA = free fatty acid HMGR = HMG CoA reductase LCAT = lecithinxholesterol acyltransferase PAP = phosphatidic acid phosphatase). (From Ref. 17 with permission.)... 

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.

Abbreviations TC, total cholesterol HDL, high density lipoprotein LDL, low density lipoprotein VLDL, very low density lipoprotein TG, triglycerides CETP, cholesteryl ester transfer protein FC, free cholesterol EC, esterified cholesterol BW, body weight BWG, body weight gain AIN, American Institute of Nutrition Tg, transgenic LF, low fat SEA, saturated fatty acids MUFA monoun-saturated fatty acids PUFA polyunsaturated fatty acids ND, not detectable. 

The esterification of cholesterol in animals has attracted considerable research because of the possible involvement of cholesterol and its ester in various disease states (cf. Glomset and Norum, 1973, and Sections 12.1, 12.3 and 12.6). Cholesterol esters are formed by the action of lecithin cholesterol acyltransferase (LCAT, EC 2.3.1.43) which is particularly active in plasma (cf. Sabine, 1977, for a review of cholesterol metabolism). The reaction involves transfer of a fatty acid from position 2 of lecithin (phosphatidylcholine) to the 3-hydroxyl group of cholesterol with the formation of monoacyl-phosphatidylcholine. Although LCAT esterifies plasma cholesterol solely at the interface of high-density lipoprotein and very-low-density lipoprotein, the cholesterol esters are transferred to other lipoproteins by a particular transport protein (CETP cholesteryl ester transfer protein). Cholesteryl esters, in contrast to free cholesterol, are taken up by cells mostly via specific receptor pathways (Brown et aL, 1981), are hydrolysed by lysosomal enzymes and eventually re-esterified and stored within cells. LCAT may also participate in the movement of cholesterol out of cells by esterifying excess cholesterol in the intravascular circulation (cf. Marcel, 1982). 

C, cholesterol CM, chylomicrons CETP, cholesteryl ester transfer protein HDL, LDL, VLDL, high-, low-, and very-low-density lipoprotein LCAT, lecithin-cholesterol acyltransferase LPL, lipoprotein lipase TAG, triacylglycerol. 

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