Lipidic epoxidation

There is also an enzyme for removal of methyl and ethyl groups from bases by oxidizing them to their respective aldehydes-the Aik B repair enzyme. Lipid epoxides, which may be produced in inflammatory tissue and can yield alkylated bases, will also be repaired by this enzyme (Fig. 6.47). Metabolic activation of vinyl chloride will also yield the same adduct (see chap. 7). 

The titanium compounds CpTiCl3, Cp2TiCl2, and CH2(C5H4)2TiCl2 have been used as catalysts for the diastereoselective epoxidation of allylic alcohols.1932 [TiCp2(LL)]2+ (LL = 1,10-phenantroline, 2,2 -bipyridine) (Scheme 758) have been studied in order to determine the importance of the ancillary chelated ligands versus the metal center for the membrane-permeabilizing action and their effects on lipid epoxidation reactions.1933... 

Mori et al. have demonstrated the most dramatic uses of lithiated epoxides in natural product synthesis [62]. By employing the chemistry developed by Jackson, and subsequently performing a Lewis acid-catalyzed (BF3 OEt2) cyclisation, tetra-hydrofuran, tetrahydropyran, and oxepane rings are readily accessed this strategy is demonstrated by the synthesis of the marine epoxy lipid 173 (Scheme 5.40) [63]. 

Monooxygenases. Under nonlignolytic conditions, arene monooxygenase and epoxide hydrolase systems may function to produce trani-dihydrodiols. Hydrogen abstraction mediated by the lipid peroxidase system may operate, for example, in the formation of fluorene-9-one from fluorene by Ph. chrysosporium (Bogan et al. 1996). 

Arene oxides and diol epoxides are generally unstable in aqueous, especially acidic media (103-105). and in addition, several groups have noted that DNA has a marked catalytic effect upon diol epoxide hydrolysis (106.107). However, in cells there appears to be sites, probably lipid in nature, in which these compounds can have much longer half-lives. 

Peroxyl radicals are the species that propagate autoxidation of the unsaturated fatty acid residues of phospholipids (50). In addition, peroxyl radicals are intermediates in the metabolism of certain drugs such as phenylbutazone (51). Epoxidation of BP-7,8-dihydrodiol has been detected during lipid peroxidation induced in rat liver microsomes by ascorbate or NADPH and during the peroxidatic oxidation of phenylbutazone (52,53). These findings suggest that peroxyl radical-mediated epoxidation of BP-7,8-dihydrodiol is general and may serve as the prototype for similar epoxidations of other olefins in a variety of biochemical systems. In addition, peroxyl radical-dependent epoxidation of BP-7,8-dihydrodiol exhibits the same stereochemistry as the arachidonic acid-stimulated epoxidation by ram seminal vesicle microsomes. This not only provides additional... 

It has been proposed [2] (Figure 24.1) that after binding to cytochrome, the substrates such as epoxides, A-oxides, nitro compounds, and lipid hydroperoxides accept two electrons and are reduced to the compounds RH(H)2. In contrast, the oxidizable substrates react with the oxygenated P-450 complex (RH)Fe2+02 (RH)Fe3+ 02 -. After transfer the second electron substrate RH is hydroxylated to ROH and cytochrome P-450 is oxidized to the starting Fe3+ state, completing the catalytic cycle. It is possible that hydroxylation proceeds through the formation of hydroxyl and carbon radicals [3], but a true role of free radicals at the final stages of hydroxylation is still obscure. 

Polyunsaturated (dienes and trienes) lipids found in sediments have been proven to be valuable tools in the determination of palaeo-water temperatures616-18. These C20, C25 and C30 highly branched isoprenoids were investigated analytically by all the tools suggested in this review. We will select one diene to demonstrate the use of the MS, oxidation (bis-epoxidation) MS and H NMR techniques previously discussed. This diene, 2,6,10,14-tetramethyl-7-(3-methylpent-4-enyl)pentadec-5-ene (4), shows the fragmentation pattern given in Scheme 2. 

The health impairing and toxic elfects of oxidation of lipids are due to loss of vitamins, polyenoic fatty acids, and other nutritionally essential components formation of radicals, hydroperoxides, aldehydes, epoxides, dimers, and polymers and participation of the secondary products in initiation of oxidation of proteins and in the Maillard reaction. Dilferent oxysterols have been shown in vitro and in vivo to have atherogenic, mutagenic, carcinogenic, angiotoxic, and cytotoxic properties, as well as the ability to inhibit cholesterol synthesis (Tai et ah, 1999 Wpsowicz, 2002). 

Heptachlor epoxide was measured in a strip of skin, fat, and subcutaneous tissue from 68 children who died in the perinatal period and ranged from not detected (nondetectable) to 0.563 ppm (mean 0.173) (Zavon et al. 1969). In 10 other stillborn infants, heptachlor epoxide levels measured in various tissues were as follows brain (nondetectable), lung (0.17 0.07 ppm), adipose (0.32 0.10 ppm), spleen (0.35 0.08 ppm), liver (0.68 0.50 ppm), kidney (0.70 0.28 ppm), adrenal (0.73 0.27 ppm), and heart (0.80 0.30 ppm) (Curley et al. 1969). In another study, the following heptachlor epoxide levels were measured in extracted lipids from mothers and newborn infants maternal adipose tissue (0.28 0.31 ppm), maternal blood (0.28 0.46 ppm), uterine muscle (0.49 0.51 ppm), fetal blood (1.00 0.95 ppm), placenta (0.50 0.40 ppm), and amniotic fluid (0.67 1.16 ppm) (Polishuk et al. 1977a). These data provide evidence of transplacental transfer to the fetus. 

There are data from animal studies in mice, rats, and pigs that indicate that both carbohydrate metabolism and lipid metabolism may be affected by exposure to heptachlor or heptachlor epoxide (Enan et al. 1982 Halacka et al. 1974 Kacew and Singhal 1973 Pelikan 1971). Alterations in gluconeogenic enzymes and an increase in cellular steatosis in the liver have been reported. Granulomas and fibrotic liver have also been observed. In addition, hepatocellular carcinoma was identified as causally related to heptachlor in the diet in a mouse study conducted by the National Cancer Institute (NCI 1977). The existing evidence suggests that heptachlor and heptachlor epoxide are hepatic toxicants. 

Heptachlor and heptachlor epoxide have been measured in samples of human milk using GC/ECD and GC/MS (Mussalo-Rauhamaa et al. 1988 Polishuk et al. 1977b Ritcey et al. 1972). Sample preparation steps for milk involve homogenization with chloroform/methanol, lipid extraction with petroleum ether, hexane or acetone-hexane, clean-up by column chromatography, and elution with acetonitrile, hexane, methylene chloride, or dichloromethane-petroleum ether. Precision, accuracy, and sensitivity were not reported for most of the studies however, one study reported a sensitivity in the low-ppb range (Ritcey et al. 1972). 

While it is well established that HO—ONO can be involved in such two-electron processes as alkene epoxidation and the oxidation of amines, sulfides and phosphines, the controversy remains concerning the mechanism of HO-ONO oxidation of saturated hydrocarbons. Rank and coworkers advanced the hypothesis that the reactive species in hydrocarbon oxidations by peroxynitrous acid, and in lipid peroxidation in the presence of air, is the discrete hydroxyl radical formed in the homolysis of HO—ONO. The HO—ONO oxidation of methane (equation 7) on the restricted surface with the B3LYP and QCISD methods gave about the same activation energy (31 3 kcalmol" ) irrespective of basis set size . ... 

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