0-Lipoproteins, plasma

The plasma lipoproteins can be divided into various low density (LDL) and high density (HDL) varieties, the latter having the highest phospholipid content (Table 11.7). 

Low-density lipoproteins are the migor carriers of cholesterol in the blood. They consist of a core of cholesterol ester molecnles surrounded by a coat of phospholipid molecules, which in turn is wrapped in a single apolipoprotein. Blood also contains what are called chylomicrons. These have a very low phospholipid content and consist mainly of a core of triglycerides coated with a thin layer of protein. 

The ether derivative (11.4) of phosphatidyl choline is a powerful platelet-activating factor. Concentrations as low as 10 M in the blood will cause aggregation of platelets and the dilation of blood vessels. 

Blood plasma contains a number of soluble lipoproteins, which are classified, according to their densities, into four major types. These lipid-protein complexes function as a lipid transport system. Isolated lipids are insoluble in blood, but they are rendered soluble, and therefore transportable, by combination with specific proteins, the so-called lipoproteins. There are four basic types in human blood (1) chylomicrons, (2) very low density lipoproteins (VLDL), (3) low-density lipoproteins (LDL). and (4) high-density lipoproteins (HDL). Their properties are summarized in Table 6.2. 

The different compositions of the plasma lipoproteins give a clue to their function. Essentially, those lipoproteins rich in TAGs are synthesized by the liver (VLDL) and small intestine (chylomicrons) and deliver the neutral fat to extrahepatic tissues (particularly adipose tissue). The fat-depleted lipoproteins have a higher density, and are involved in essential cholesterol transfers. 

Question What is the general structure of a lipoprotein particle  

See Fig. 6-4. The polar surface of the spherical particle renders the assembly soluble in water. This structure can be considered to be a tentative one only. The amount of polar material in chylomicrons and VLDL is astonishingly small. Moreover, when lipoproteins come into contact with the membranes of the cells of target tissue, the proteins remain soluble and do not become incorporated into the membrane. This suggests that the proteins of lipoproteins have unusual properties. It is known that several species of proteins (apoproteins AI, All. B4K, B1(K), Cl, CII, CIII, D, and E) occur. The amino acid sequences of some of them have been determined, and they possess hydrophobic regions i.e., they have properties suggesting that parts of their structure are compatible with hydrocarbons (e.g., TAGs and the tails of phospholipids). 

When water is added to certain dry phospholipids with long hydrocarbon chains, the phospholipids swell, and when they are dispersed in more water, structures known as liposomes are formed. Liposomes are vesicles with multilayers of phospholipid. See Fig. 6-5. When subjected to ultrasonic vibration (sonication), liposomes are transformed into vesicles that have only a single bilayer of phospholipid. 

Cholesterol, which is largely insoluble in aqueous m a, travels through the blood circulation in the form of Upoprotein complexes. The plasma lipoproteins are a family of globular particles that share common structural features. A core of hydrophobic lipid, principally triacylglycerols (triglycerides) and cholesterol esters, is surrounded by a hydrophilic monolayer of phospholipid and protein (the apolipoproteins) [1-3]. Lipid-apolipoprotein interactions, facihtated byi amphi-pathic protein helices that segregate polar from nonpolar surfaces [2,3], provide the mechanism by which cholesterol can circulate in a soluble form. In addition, the apolipoproteins modulate the activities of certain enzymes involved in Upoprotein metabolism and interact with specific cell surface receptors which take up Upopro-teins by receptor-mediated endocytosis. Differences in the Upid and apoUpoprotein compositions of plasma Upoproteins determine their target sites and classification based on buoyant density. 

Four main classes of Upoproteins are present in normal human plasma (for reviews, see refs. 1-3). The largest of these, the chylomicrons (diameter 800-5000 A, density 0.95 g/ml they remain at the origin during electrophoresis. Fig. 1), contain predominantly dietary triglycerides and a spectrum of apoUpoproteins (Fig. 2). Chylomicrons are manufactured in the intestines from dietary Upids, secreted into the lymph, and subsequently enter the blood circulation. Since chylomicrons are too large to cross the vascular endothelium, they are degraded in plasma by the enzyme Upoprotein lipase which is present on the surface of endotheUal cells that 

Very-low-density lipoproteins (VLDL) are large particles (diameter 300-900 A, density range 0.95-1.006 g/ml, pre-]8 electrophoretic mobility, Fig. 1) in which triacylglycerols predominate. VLDL contain 8-10% protein (predominantly apo-B and apo-E, see Fig. 2) and 90-92% lipid (triacylglycerols 56%, phospholipids 19-21%, cholesterol and cholesterol esters 17% [6]). VLDL are synthesized in the 

LDL (diameter 200-250 A, density range 1.019-1.063 g/ml, /8-electrophoretic mobility, Fig. 1) are often termed )8-lipoproteins. LDL contain, by weight, 75% lipid (principally esterified cholesterol) and 25% protein which consists exclusively of apo-B (Fig. 2). LDL is the major vehicle for transport of cholesterol to peripheral tissues and normally accounts for about 70% of total plasma cholesterol [10]. LDL metabolism is of medical interest since there is a direct correlation between increased plasma LDL concentration and an increased incidence of atherosclerotic heart disease [11]. 

the smallest of the lipoprotein particles (diameter 80-120 A, density range 1.063-1.210 g/ml, a-electrophoretic mobility. Fig. 1), constitute a heterogeneous class of lipoproteins that contain various subclasses of apolipoproteins (Fig. 2). 

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LIPOPROTEINS. Blood plasma lipoproteins are prominent examples of the class of proteins conjugated with lipid. The plasma lipoproteins function primarily in the transport of lipids to sites of active membrane synthesis. Serum levels of low density lipoproteins (LDLs) are often used as a clinical index of susceptibility to vascular disease. 

Lipoproteins contain lipid Blood plasma lipoproteins ... 

Plasma lipid transfer proteins, which include the cholesteryl-ester-transfer-protein (CETP previously known as lipid transfer protein I, LTP-I) and the phospholipid-transfer-protein (PLTP previously known as lipid transfer protein II, LTP-II) mediate the transfer of lipids (cholesteryl esters, triglycerides and phospholipids) between lipoproteins present in human plasma. These proteins significantly affect plasma lipoprotein concentration and composition. 

Segrest MP et al The amphipathic alpha-helix A multifunctional structural motif in plasma lipoproteins. Adv Protein Chem... 

Cholesterol (Figure 14-17) is widely distributed in all cells of the body but particularly in nervous tissue. It is a major constituent of the plasma membrane and of plasma lipoproteins. It is often found as cholesteryl ester, where the hydroxyl group on position 3 is esteri-fied with a long-chain fatty acid. It occurs in animals but not in plants. 

Four Major Groups of Plasma Lipoproteins Have Been Identified... 

Figure 2S-1. Generalized structure of a plasma lipoprotein. The similarities with the structure of the plasma membrane are to be noted. Small amounts of cholesteryl ester and triacylglycerol are to be found in the surface layer and a little free cholesterol in the core.

The second type of fatty liver is usually due to a metabolic block in the production of plasma lipoproteins, thus allowing triacylglycerol to accumulate. Theoretically, the lesion may be due to (1) a block in apolipoprotein synthesis, (2) a block in the synthesis of the lipoprotein from lipid and apolipoprotein, (3) a failure in provision of phospholipids that are found in lipoproteins, or (4) a failure in the secretory mechanism itself. 

CHOLESTEROL IS TRANSPORTED BETWEEN TISSUES IN PLASMA LIPOPROTEINS (Figure 26-6)... 

Vitamin E is the Major Lipid-Soluble Antioxidant in Cell Membranes Plasma Lipoproteins... 

The main function of vitamin E is as a chain-breaking, free radical trapping antioxidant in cell membranes and plasma lipoproteins. It reacts with the lipid peroxide radicals formed by peroxidation of polyunsaturated fatty acids before they can establish a chain reaction. The tocopheroxyl free radical product is relatively unreactive and ultimately forms nonradical compounds. Commonly, the tocopheroxyl radical is... 

In contrast with the hydrocarbon carotenes primarily located in the cores of the CM particles, xanthophylls are present at the surfaces of the CM particles, making their exchanges with other plasma lipoproteins easier." Therefore, if some exchanges occur between lipoproteins, AUC (or absorption) values of the newly absorbed compound in the TRL fraction will be underestimated. Based on all these considerations, the present approach is more appropriate to determine the relative bioavailability of a compound derived from various treatments within one snbject and/or within one study. 

In fasting hnman sernm, the hydrocarbon carotenes (P-carotene and lycopene) are fonnd primarily in LDL, while the xanthophylls (Intein, zeaxanthin, and P-cryptox-anthin) are more evenly distribnted between LDLs and HDLs. As mentioned earlier and contrary to the carotenes, the xanthophylls are primarily located at the surfaces of lipoprotein particles, making them more likely to exchange between plasma lipoproteins. This hypothesis may explain their eqnal distribntion (or apparent equilibrinm) between LDLs and HDLs. 

Tyssandier, V. et al.. Carotenoids, mostly the xanthophylls, exchange between plasma lipoproteins, Int. J. Vitam. Nutr. Res., 72, 300, 2002. 

Clevidence, B.A. and Bieri, J.G., Association of carotenoids with human plasma lipoproteins, Methods Enzymol, 214, 33, 1993. 

Sterlie, M, Bjerkeng, B., and Liaaen-Jensen, S., Blood appearance and distribution of astaxanthin E/Z isomers among plasma lipoproteins in humans administered a single meal with astaxanthin, m Abstracts of 12th International Carotenoid Symposium, Cairns, Australia, Abstract 2A-13, 1999, 72. 

D. M. Small, in Plasma Lipoproteins and Coronary Artery Disease (R. A. Kreisberg and J. P. Segrest, eds.), Blackwell Scientific Publications, London, 1992, pp. 57-91. 

Han KH, Han KO, Green SR, Quehenberger O. Expression of the monocyte chemoattractant protein-1 receptor CCR2 is increased in hypercholesterolemia. Differential effects of plasma lipoproteins on monocyte function. J Lipid Res 1999 40(6) 1053-1063. 

Superko, H., Bortz, W., Williams, P., Albers, J. and Wood, P., Caffeinated and decaffeinated coffee effects on plasma lipoprotein cholestrol, apolipoprotiens and lipase activity A controlled, randomized trial. American Journal of Clinical Nutrition 54, 599-605, 1991. 

FIGURE 24.1 The pathway of carotenoid transport in the silkworm. Carotenoids are absorbed from dietary mulberry leaves into the intestinal mucosa, transferred to the hemolymph (1), transported in the hemolymph by plasma lipoproteins (2), and accumulated in the silk gland (3). 

Hyperlipemia may manifest itself by an increased concentration of lipids, or certain groups thereof. For example, hypercholesterolemia and hypertriglyceri-demia may be mentioned in this connection. Since practically all the blood plasma lipids make part of lipoproteins, hyperlipemias may be reduced to one of the hyper-lipoproteinemia forms which differ in the varied ratios of plasma lipoproteins of different groups. 

Volume 128. Plasma Lipoproteins (Part A Preparation, Structure, and Molecular Biology)... 

Volume 129. Plasma Lipoproteins (Part B Characterization, Cell Biology, and Metabolism)... 

Which subpopulations of blood plasma lipoproteins bind the wine-derived antioxidants ... 

An important characteristic of mammalian 15-LOX is its capacity to oxidize the esters of unsaturated acid in biological membranes and plasma lipoproteins without their hydrolysis to free acids. Jung et al. [19] found that human leukocyte 15-LOX oxidized phosphatidylcholine at carbon-15 of the AA moiety. Soybean and rabbit reticulocyte 15-LOXs were also active while human leukocyte 5-LOX, rat basophilic leukemia cell 5-LOX, and rabbit platelet 12-LOX were inactive. It was suggested that the oxygenation of phospholipid is a unique property of 15-LOX. However, Murray and Brash [20] showed that rabbit reticulocyte... 

The structure activity relationship (SAR) and animal model studies of biaryl benzamide MTP inhibitors 3 and 4 have also been reported. Compound 3 has an IC50 of 0.5 nM against human MTP in an in vitro assay and showed normalization of plasma lipoprotein levels in Watanabe-heritable hyperlipidemic rabbits,... 

The albumin and non-esterified fatty acid complexes (99 1) constitute only about 5% of all plasma lipoprotein. 

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