Cholesteryl formate

Figure 25. Inverse of selective reflection maxima (o=p) as a function of composition for a number of binary chiral nematic mixtures. Here the components are O cholesteryl formate/cholesteryl chloride (at 50 °C), A cholesteryl propionate/cholesteryl chloride (at60°C), cholesteryl heptanoate/cholesteryl chloride (at 60 °C), A cholesteryl laurate/cholesteryl chloride (at 60°C) [105],...

Steroids. The complex from equimolar amounts of dimethylformamide and phosgene, which is readily formed in situ or in dry benzene with loss of GOg, is an excellent formylating agent for steroid alcohols.— E Dimethylformamide-phosgene complex added in one portion to a soln. of cholesterol in dimethylformamide, shaken 5-10 min. at room temp., then poured on ice cholesteryl formate. Y 98%. F. e. s. K. Morita, S. Noguchi, and M. Nishikawa, Ghem. Pharm. Bull. 7, 896 (1959). 

The displacement of homoallylic tosylates follows an entirely different course with a strong tendency for the formation of cyclo steroids. Thus, when the 3/ -tosylate of a A -steroid (187) is treated with lithium aluminum deuteride, the product consists mainly of a 3l3-di-A -steroid (188) and a 6c-dj-3,5a-cyclo steroid (189). The incorporation of deuterium at the 3 -position in (188) indicates that this reaction proceeds via a 3,5-cyclo cholesteryl cation instead of the usual S, 2 type displacement sequence. This is further substantiated by the formation of the cyclo steroid (189) in which the deuterium at C-6 is probably in the p configuration. ... 

For the separation of amino acids, the applicability of this principle has been explored. For the separation of racemic phenylalanine, an amphiphilic amino acid derivative, 1-5-cholesteryl glutamate (14) has been used as a chiral co-surfactant in micelles of the nonionic surfactant Serdox NNP 10. Copper(II) ions are added for the formation of ternary complexes between phenylalanine and the amino acid cosurfactant. The basis for the separation is the difference in stability between the ternary complexes formed with d- or 1-phenylalanine, respectively. The basic principle of this process is shown in Fig. 5-17 [72]. 

Reaction with lipoprotein lipase results in the loss of approximately 90% of the triacylglycerol of chylomicrons and in the loss of apo C (which remrns to HDL) but not apo E, which is retained. The resulting chy-lotnicron remnant is about half the diameter of the parent chylomicron and is relatively enriched in cholesterol and cholesteryl esters because of the loss of triacylglycerol (Figure 25-3). Similar changes occur to VLDL, with the formation of VLDL remnants or IDL (intermediate-density lipoprotein) (Figure 25-4). 

It follows from the above that the neutrophil-mediated LDL oxidation may occur by both NADPH oxidase- and MPO-dependent mechanisms. It was recently demonstrated [162] that the rates of formation of phosphatidylcholine and cholesteryl ester hydroperoxides during LDL oxidation by PMA-stimulated neutrophils of MPO-knockout mice were about 66% and 44% of those by wild-type neutrophils. In both cases LDL oxidation was inhibited by SOD. These findings suggest that superoxide mediates both NADPH oxidase- and MPO-dependent pathways of oxidation by stimulated neutrophils. 

Belkner et al. [32] demonstrated that 15-LOX oxidized preferably LDL cholesterol esters. Even in the presence of free linoleic acid, cholesteryl linoleate continued to be a major LOX substrate. It was also found that the depletion of LDL from a-tocopherol has not prevented the LDL oxidation. This is of a special interest in connection with the role of a-tocopherol in LDL oxidation. As the majority of cholesteryl esters is normally buried in the core of a lipoprotein particle and cannot be directly oxidized by LOX, it has been suggested that LDL oxidation might be initiated by a-tocopheryl radical formed during the oxidation of a-tocopherol [33,34]. Correspondingly, it was concluded that the oxidation of LDL by soybean and recombinant human 15-LOXs may occur by two pathways (a) LDL-free fatty acids are oxidized enzymatically with the formation of a-tocopheryl radical, and (b) the a-tocopheryl-mediated oxidation of cholesteryl esters occurs via a nonenzymatic way. Pro and con proofs related to the prooxidant role of a-tocopherol were considered in Chapter 25 in connection with the study of nonenzymatic lipid oxidation and in Chapter 29 dedicated to antioxidants. It should be stressed that comparison of the possible effects of a-tocopherol and nitric oxide on LDL oxidation does not support importance of a-tocopherol prooxidant activity. It should be mentioned that the above data describing the activity of cholesteryl esters in LDL oxidation are in contradiction with some earlier results. Thus in 1988, Sparrow et al. [35] suggested that the 15-LOX-catalyzed oxidation of LDL is accelerated in the presence of phospholipase A2, i.e., the hydrolysis of cholesterol esters is an important step in LDL oxidation. 

One role of high density lipoprotein (HDL) is to collect unesterified cholesterol from cells, including endothelial cells of the artery walls, and return it to the liver where it can not only inhibit cholesterol synthesis but also provide the precursor for bile acid formation. The process is known as reverse cholesterol transfer and its overall effect is to lower the amount of cholesterol in cells and in the blood. Even an excessive intracellular level of cholesterol can be lowered by this reverse transfer process (Figure 22.10). Unfortunately, the level of HDL in the subendothelial space of the arteries is very low, so that this safety valve is not available and all the cholesterol in this space is taken up by the macrophage to form cholesteryl ester. This is then locked within the macrophage (i.e. not available to HDL) and causes damage and then death of the cells, as described above. 

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

LDL is catabolized chiefly in hepatocytes and other cells by receptor-mediated endocytosis. Cholesteryl esters from LDL are hydrolyzed, yielding free cholesterol for the synthesis of cell membranes. Cells also obtain cholesterol by synthesis via a pathway involving the formation of mevalonic acid by HMG-CoA reductase. Production of this enzyme and of LDL receptors is transcriptionally regulated by the content of cholesterol in the cell. Normally, about 70% of LDL is removed from plasma by hepatocytes. Even more cholesterol is delivered to the liver via IDL and chylomicrons. Unlike other cells,... 

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