Cholesteryl arachidonate

Cholesteryl arachidonate, hydroperoxide formation, 693 Cholesteryl esters... 

Figure 4. Normal phase high-pressure liquid chromatography of cholesterol esters isolated from atherosclerotic lesions of human aorta (I), free cholesterol (II), oxygenated cholesterol esters (III), cholesteryl arachidonate (IV), cholesteryl linoleate (V), cholesteryl oleate and cholesteryl palmitate.

Figure 5. The oxygenation of cholesteryl arachidonate by animal or plant C-15 lipoxygenases (1), oxidation by rabbit reticulocyte lipoxygenase (2), oxidation by soybean lipoxygenase.

The CE of other plasma hpoproteins can be cleared from the plasma by both receptor-dependent and receptor-independent mechanisms. VLDL and LDL can bind to the apo B/E receptors that are present on the surfaces of many cells (see Chapter 2). These receptors mediate internalization of VLDL and LDL, a process that soon leads to CE degradation. They also mediate the uptake and degradation of HDL that contain apo E. The CE of apo E-free HDL seem, on the other hand, to be cleared by a different mechanism. Apo E-free HDL can bind to receptors that recognize apo AI, whereupon mechanisms that do not necessarily involve the uptake and degradation of the whole lipoprotein particle can mediate CE uptake. These mechanisms may operate in adrenal cells [88], and conceivably may be involved also in the uptake of HDL cholesteryl arachidonate by endothelial cells [89]. 

The levels of palmitic acid, palmitoleic acid, stearic acid and oleic acid increased in both groups, after 4 h of copper-oxidation. While concentrations of cholesteryl oleate, cholesteryl linoleate, cholesteryl arachidonate and cholesteryl docosahexanoate were reduced, following copper stimulated oxidation, in both groups [85]. 

Some of the cholesterol esterases used in these analytical systems show varying degrees of specificity toward the different cholesterol esters, and problems have occurred when these reagents are used for several species. For example, in rats, where there is a fivefold-higher concentration of cholesteryl arachidonate ester compared to human plasma, plasma cholesterol may be underestimated with some reagents (Demacker et al. 1983 Noel, Dupras, and Pillion 1983 Wiebe and Bernert 1984 Evans 1986). 

Yin, H., Havrilla, C. M., Morrow, J. D and Porter, N. A. 2002. Formation of isoprostane bicyclic endoperoxides from the autoxidation of cholesteryl arachidonate,... 

Sevanian et al. (1994) applied GLC and LC/TS/MS for the analysis of plasma cholesterol-7-hydroperoxides and 7-ketocholesterol. Analysis of human and rabbit plasma identified the commonly occurring oxidation products, yet dramatic increases in 7-ketocholesterol and cholesterol-5p, 6P-epoxide were observed. The study failed to reveal the presence of choles-terol-7-hydroperoxides, which were either too unstable for isolation, metabolized or further decomposed. The principal ions of cholesterol oxides monitored by LC/TS/MS were m/z 438 (cholestane triol) m/z 401 (cholesterol-7-hydroperoxide) m/z 401 (7-ketocholesterol) m/z 367 (7a-hydroxycholesterol) m/z 399 (cholesta-3,5-dien-7-one) and m/z 385 (choles-terol-5a,6a-epoxide). The major ions were supported by minor ions consistent with the steroid structure. Kamido et al. (1992a, b) synthesized the cholesteryl 5-oxovaleroyl and 9-oxononanoyl esters as stable secondary oxidation products of cholesteryl arachidonate and linoleate, respectively. These compounds were identified as the 3,5-dinitrophenylhydrazone (DNPH) derivatives by reversed-phase LC/NICI/MS. These standards were used to identify cholesteryl and 7-ketocholesteryl 5-oxovaleroyl and 9-oxononanoyl esters as major components of the cholesteryl ester core aldehydes generated by copper-catalysed peroxidation of low-density lipoprotein (LDL). In addition to 9-oxoalkanoate (major product), minor amounts of the 8, 9, 10, 11 and 12 oxo-alkanoates were also identified among the peroxidation products of cholesteryl linoleate. Peroxidation of cholesteryl arachidonate yielded the 4, 6, 7, 8, 9 and 10 oxo-alkanoates of cholesterol as minor products. The oxysterols resulting from the peroxidation of the steroid ring were mainly 7-keto, 7a-hydroxy and 7P-... 

The total serum cholesterol amounts to about 150—200 mg %, more than three quarters of which is esterified predominantly with long chain unsaturated fatty acids (18 1,18 2,20 4) The structure of cholesteryl arachidonate is given in the next figure ... 

Fig. 11.6.1. HPLC separation of cholesterol and cholesteryl ester standards. Chromatographic conditions column, Supelcosil LC-18 (250x4.6 mm I.D.) mobile phase, acetonitrile-methanol-chloroform (1 1 1, v/v/v) flow rate, 1.0 ml/min temperature, ambient detection, differential refractometer. Peaks 1, cholesterol, 2, acetate 3, propionate 4, butyrate 5, nonanoate 6, decanoate 7, arachidonate 8, laurate 9, linoleate 10, oleate 11, elaidate 12, palmitate 13, stearate. The average mass of lipid chromatographed was 20-40 ng. Reproduced from Perkins et al. (1981), with...

Nitrogen dioxide Nitro-arachidonic acid Cholesteryl nitro-linoleate Conjugated nitrolinoleic acid Nitro fatty acids Nitro-linoleic acid Nitro-oleic acid Nitric oxide synthase Inducible nitric oxide synthase... 

Phinney SD, Odin RS, Johnson SB, Holman RT. Reduced arachidonate in serum phospholipids and cholesteryl esters associated with vegetarian diets in humans. Am J Clin Nutr 1990 51 385-392. 

Other methods used to measure LDL oxidation include the loss of hnoleic acid (18 2), arachidonic acid (20 4) and cholesteryl esters, formation of conjugated dienes and TBARS, and electrophoretic mobility. The loss of 18 2,20 4... 

Fig. 2.3. Overview of arachidonoyl-CoA metabolism in mammalian cells. Four major metabolic routes are illustrated ( ) formation of phospholipids (2) formation of triacylglycerols (3) formation of cholesteryl esters (4) hydrolysis. Arachidonate stored in triacylglycerol may become available for incorporation into phospholipid through the action of the enzyme triacylglycerol lipase.

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