Removal of lipid hydroperoxides

Lipid hydroperoxides arise in membranes and in oxidised LDL as a direct consequence of the intervention by a-T in terminating chain reactions, as well as from the chain reactions themselves. The possibility exists that catalysis by divalent transition metal cation complexes may cause the re-formation of lipid-peroxyl radicals or of other radical species such as the alkoxyl radical. The rate of reaction of Fe3+ with lipid hydroperoxides is much slower than the rate of 

Considerable interest was generated when it was shown that substantial GSHPx activity exists in liver of selenium-depleted rats when LOOH is used as substrate but not H2O2 [20]. The enzyme was subsequently shown to be identical to a member of the glutathione-S-transferase family of enzymes [20,21,48], The enzyme was for a time called selenium-independent , or non-selenium dependent GSHPx and this nomenclature, which is confusing, has persisted in the literature. The role of GSH-S-transferases in the overall protection of cells against the harmful potential of LOOH has not been determined but it undoubtedly must form part of that protective mechanism. 

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Hydroperoxides are removed from bonds in damaged phospholipid by activated phospholipase Aj and free hydroperoxide becomes a substrate for peroxidases. Otherwise, the oxidation of fatty acids results in the accumulation of lipid hydroperoxides and their secondary metabolites such as ( )-4-hydroxynon-2-enal and malondialdehyde, which react with proteins and DNA (see Section 3.8.1.12.1). 

The mechanism of NPYR formation has been studied by Coleman (37) and Bharucha et al. ( ). Coleman (37) reported that the requirement for a high temperature, the inhibitory effects of water and antioxidants, and the catalytic effect of a lipid hydroperoxide are consistent with the involvement of a free radical in the formation of NPYR. Similarly, Bharucha et al. (29) suggested that, since both NPYR and NDMA increase substantially towards the end of the frying process, N-nitros-amine formation during frying of bacon occurs essentially, if not entirely, in the fat phase after the bulk of the water is removed and therefore by a radical rather than an ionic mechanism. These authors speculated that, during the frying of... 

Contrary to LDL, high-density lipoproteins (HDL) prevent atherosclerosis, and therefore, their plasma levels inversely correlate with the risk of developing coronary artery disease. HDL antiatherogenic activity is apparently due to the removal of cholesterol from peripheral tissues and its transport to the liver for excretion. In addition, HDL acts as antioxidants, inhibiting copper- or endothelial cell-induced LDL oxidation [180], It was found that HDL lipids are oxidized easier than LDL lipids by peroxyl radicals [181]. HDL also protects LDL by the reduction of cholesteryl ester hydroperoxides to corresponding hydroperoxides. During this process, HDL specific methionine residues in apolipoproteins AI and All are oxidized [182]. 

Lipid hydroperoxides can be removed by reaction with GSH catalyzed by GSH peroxidase. The enzyme phospholipase A2 has been proposed to have a role in the detoxication of phospholipid hydroperoxides by releasing fatty acids from peroxidized membranes. 

Lipid radicals and other radicals may be removed by a number of endogenous compounds as well as glutathione. One is vitamin E (a-tocopherol), which reacts with lipid hydroperoxide radicals to yield the hydroperoxide and a-tocopherol quinone ... 

Caeruloplasmin can remove both hydrogen peroxide and lipid hydroperoxides at physiologically relevant concentrations of reduced glutathione loiown to be present in lung and lung lining fluid (Park et al. 1999). 

The free radical reaction may be accelerated and propagated via chain branching or homolytical fission of hydroperoxides formed to generate more free radicals (equations (11.4), (11.5)). Free radicals formed can initiate or promote fatty acid oxidation at a faster rate. Thus, once initiated, the free radical reaction is self-sustaining and capable of oxidizing large amounts of lipids. On the other hand, the free radical chain reaction may be terminated by antioxidants (AH) such as vitamin E (tocopherols) that competitively react with a peroxy radical and remove a free radical from the system (equation (11.6)). Also, the chain reaction may be terminated by self-quenching or pol)rmerization of free radicals to form non-radical dimers, trimers and polymers (equation (11.7)). 

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