Plasma lipoproteins, properties

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... 

Chromatographic procedures have been applied increasingly in the fractionation and purification of plasma lipoproteins (Bll, L3, W2). Agarose media have proved to be particularly valuable because of their sieving properties for particles in the size range of plasma lipoproteins, including the low- and very low-density classes (SI). 

Relevant heparin-binding enzymes not involved in the coagulation cascade are, for example, elastase, cathepsin G, superoxide dismutase, lipoprotein lipase and other lipases. The plasma clearing properties of heparin are associated with its binding to lipoprotein lipase and hepatic lipase when the enzymes are released from the surface of endothelial cells [11] and have been studied in view of a potential impact on the regulation of atherosclerosis. 

TABLE 21-2 Major Classes of Human Plasma Lipoproteins Some Properties... 

Current opinion suggests that after emptying into the bloodstream, drugs associated with lymph lipoproteins equilibrate across the various plasma lipoprotein and protein fractions and take on the same clearance properties as drug introduced into the systemic circulation by way of the portal blood. The data of Haus et al. suggest that this is an oversimplification and that the mechanism of interconversion and interaction of dmg molecules between lymph and plasma lipoproteins is not clear [123],... 

However, the identification of increasingly lipophilic lead molecules, the physicochemical properties of which (low aqueous solubility and high log Ps) suggest a natural predisposition for increased plasma lipoprotein binding, has increased interest in the possible pharmacokinetic, therapeutic, and toxicological ramifications of drug binding to plasma lipoproteins. 

The studies that led to the lipid hypothesis measured plasma total cholesterol concentration. Cholesterol is insoluble in aqueous solution and needs to be combined with protein for transport in blood. These plasma lipoproteins are large heterogeneous aggregates that have different physical properties, such as density, chemical composition and metabolic function (Gurr et al., 2002). 

Modified (oxidized) lipid species have been identified in the plasma lipoproteins and aortic plaque of atherosclerotic humans (74, 77) and animal models (78, 79). Furthermore, the presence of COPs in circulating lipoprotein has been demonstrated in healthy humans (80) and monkeys. (73) Oxidized LDL has been proposed to have a role in foam cell formation (81) as well as having various proatherogenic properties, such as cytotoxicity and chemotactic activity (73, 82). 

Lipoproteins are macromolecular assemblies that contain proteins and lipids, including free and esterified cholesterol, triglycerides, and phospholipids. The protein components, known as apoUpoprotems, provide structural stability to the lipoproteins, and also may function as ligands in hpoprotein-receptor interactions or as cofactors in enzymatic processes that regulate lipoprotein metabolism. In aU Upoprotems, the most water-insoluble lipids (cholesteryl esters and triglycerides) are core components, and the more polar, water-soluble components (apoproteins, phospholipids, and unesterified cholesterol) are located on the surface. The major classes of lipoproteins and their properties are presented in Table 35-1. Table 35-2 describes apoproteins that have well-defined roles in plasma lipoprotein metabolism. 

LeBoeuf, R.C., Puppione, Dl,., Schumaker, VJ4., and Lusis, A J. (1983) Genetic Control of Lipid Transport in Mice. I. Structural Properties and Polymorphisms of Plasma Lipoproteins, J. Biol. Chem. 258,5063-5070. 

In 1951 Kellner et al. reported that administration of the nonionic detergents Triton A-20 or Tween 80 to rabbits and guinea pigs was followed by a sustained hyperlipemia. This observation was later extended to other animal species mice (Hirsch and Kellner, 1956a, b), rats (Friedman and Byers, 1953), and dogs (Scanu et al., 1961). Studies by Friedman and Byers (1953, 1957) and Hirsch and Kellner (1956a, b) led to the hypothesis that the hyperlipemia was secondary to the action of the detergent on the physical and chemical properties of plasma lipoproteins. Experimental support for this hypothesis was provided by the... 

Frei B., Forte T.M., Ames B.N., Cross C.E. Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Protective Effects of Ascorbic Acid. Biochem. J. 1991 277 133 8. 

Table 37.2 Plasma lipoproteins. As shown in Fig. 37.4, lipoproteins are spherical structures with a hydrophilic exterior and a hydrophobic (lipid-containing) core. Their function is to transport hpids in the hydroptulic environment of the blood. The outer surface of lipoproteins is rich in phospholipids and apolipoproteins (Table 37.1) which confer upon the lipoproteins many of their specific properties.

Edgington, T. S., and Curtiss, L. K. (1981). Plasma lipoproteins with bioregulatory properties including the capacity to regulate lymphocyte function and the immune response. Cancer Res 41 3786-3788. 

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