Metabolism of lipoproteins

Proteins embedded in the shell of lipoproteins. They serve as scaffold for assembly of the lipoprotein particle in the endoplasmic reticulum. In addition, they control metabolism of lipoproteins in the circulation by interaction with enzymes such as lipases. Finally, apolipoproteins determine cellular uptake of the particles by interaction with specific lipoprotein receptors expressed on the surface of target cells. 

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. 

A schematic representation of the metabolism of lipoproteins is shown in Fig. 12 [170]. Chylomicrons are synthesized and secreted by the small intestine. They are hydrolyzed in blood by the enzyme lipoprotein lipase... 

Nitric oxide and eicosanoid synthesis haem synthesis. The importance of the pentose phosphate pathway reduced glutathione in maintaining red cell integrity. The respiratory burst in phagocytes. Clotting and complement enzyme cascades. Metabolism of lipoproteins. 

The best-known effect of APOE is the regulation of lipid metabolism (see Fig. 10.13). APOE is a constituent of TG-rich chylomicrons, VLDL particles and their remnants, and a subclass of HDL. In addition to its role in the transport of cholesterol and the metabolism of lipoprotein particles, APOE can be involved in many other physiological and pathological processes, including immunoregu-lation, nerve regeneration, activation of lipolytic enzymes (hepatic lipase, lipoprotein lipase, lecithin cholesterol acyltransferase), ligand for several cell receptors, neuronal homeostasis, and tissue repair (488,490). APOE is essential... 

Twelve reviews cover the structure, synthesis, and metabolism of lipoproteins, regulation of cholesterol synthesis, and the enzymes LCAT and lipoprotein lipase. 

Sarria, A. J., Panini, S. R., and Evans, R. M. (1992). A functional role for vimentin intermediate filaments in the metabolism of lipoprotein-derived cholesterol in human SW-13 cells./. Biol. Chem. 267, 19455-19463. 

Marcovina SM, Morrisett JD. Structure and metabolism of lipoprotein (a). Curr Opin Lipidol 1995 6 136-45. 

Atherosclerosis and Plasma Lipids - Lipoprotein lipases play a critical role in the metabolism of lipoproteins and thus may be involved in athero-genesis. Hypercholesterolemia in the cholesterol-fed rabbit was attributed to the accumulation of chylomicron remnants, which may be formed on the aorta wall by lipoprotein lipase and deposited in the deep layers of the arterial wall without prior release into the blood stream.13 On this basis, cholesterol-rich lipoproteins in plasma may be the product rather than the cause of the atherogenic process. However, the defect in Type III hyperlipoproteinemia (broad- disease) may be ineffective removal of chylomicron remnant particles from the arterial wall,11 due to a failure of the liver to recognize such particles.15... 

In addition to receptor-mediated metabolism of lipoproteins, which is the predominant mechanism for removal of intact lipoproteins, individual components of lipoproteins, particularly unesterified cholesterol, can diffuse into cells across the plasma membrane. Other minor uptake processes include so-called fluid-phase endocytosis, which does not involve binding of lipoproteins to specific cell surface proteins, and phagocytosis, in which lipoproteins attach to the cell surface via more or less specific forces, and are subsequently engulfed by the plasma membrane. 

Apart from their operational distinction on the basis of density and lipid composition the plasma lipoprotein classes are also distinguished by the nature of the polypeptides present. The apoprotein species have been characterized and designated family names from A to H. The human plasma lipoprotein apoprotein distribution is shown in Table 12.3. Although the distribution, interchange and metabolism of lipoprotein apoproteins is extremely complicated some overall aspects of the dynamic situation can be discerned (see Schaefer etal, 1978). For example, the apoprotein content of newly synthesized VLDL and chylomicrons changes drastically as these lipoproteins enter the circulation and interact with the other lipoproteins present. Both... 

Figure 13.2. Metabolism of lipoproteins. From Gurr (1997) with permission. CE, eholesteryl esters HDL, high density lipoprotein whieh is intereonverted into two forms, HDL and HDL3 VLDL, very low density lipoprotein IDL, intermediate density lipoprotein LDL, low density lipoprotein, LCA, leeithin eholesterol aeyltransferase (see Figure 13.3).

Apolipoproteins of the C group are peptides of small molecular weights, present in chylomicrons, VLDL, IDL, and HDL. These polypeptides have common characteristics they are regulators (activators or inhibitors) of the lipid metabolism of lipoproteins, particularly the catabolism of triglyceride-rich hpoproteins [1]. The distribution of the different Apo C in lipoprotein classes varies between normal subjects and hypertriglyceridemics and in relation to fasting and the type of diet. 

Role of the Liver in the Metabolism of Lipoprotein Particles 59 Table 2. Kinetic parameters of HDL turnover in the rat... 

Yamada N, Shames DM, Stoudemire JB, Havel RJ (1986) Metabolism of lipoproteins containing apolipoprotein B 100 in blood plasma of rabbits heterogeneity related to the presence of apolipoprotein E. Proc Natl Acad Sci USA 83 3479-3483... 

Further metabolism of lipoprotein triglyceride of VLDL is accompanied by the loss of the smaller molecular weight apolipoproteins. Compared to VLDL, the proportions of apoE and apoB in IDL are increased. The most abundant apoprotein is apoC-III (Table 6). The proportion of apoC-I in IDL is increased about 3-fold compared to most VLDL. The metabolism of IDL is too poorly understood to appreciate the significance, if any, associated with its apoprotein composition. 

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