Lipid hydroperoxide glutathione peroxidase

O Donnell et al. [70] found that LOX and not cyclooxygenase, cytochrome P-450, NO synthase, NADPH oxidase, xanthine oxidase, ribonucleotide reductase, or mitochondrial respiratory chain is responsible for TNF-a-mediated apoptosis of murine fibrosarcoma cells. 15-LOX activity was found to increase sharply in heart, lung, and vascular tissues of rabbits by hypercholesterolemia [71], Schnurr et al. [72] demonstrated that there is an inverse regulation of 12/15-LOXs and phospholipid hydroperoxide glutathione peroxidases in cells, which balanced the intracellular concentration of oxidized lipids. 

Yagi, K., Komura, S., Kojima, H., Sun, Q., Nagata, N., Ohishi, N., and Nishikimi, M., 1996, Expression of human phospholipid hydroperoxide glutathione peroxidase gene for protection of host cells from lipid hydroperoxide-mediated injury. Biochem. Biophys. Res. Commun., 219 486-491... 

This selenium-dependent enzyme [EC 1.11.1.9] catalyzes the reaction of two molecules of glutathione with hydrogen peroxide to produce glutathione disulfide and two water molecules. Hydrogen peroxide can be replaced by steroid and lipid hydroperoxides, albeit not as effectively (nevertheless, this enzyme is not identical with phospholipid-hydroperoxide glutathione peroxidase [EC 1.11.1.12]). However, the hydroperoxy products formed by the action of lipoxygenase [EC 1.13.11.12] are not substrates. 

Thomas, J.P., Maiorino, M., Ursini, F. and Girotti, A.W. (1990) Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. J. Biol. Chem. 265 454-461. 

In the previous section, we have described some of the mechanisms that may lead to the fijrmation of lipid hydroperoxides or peroxyl radicals in lipids. If the peroxyl radical is formed, then this will lead to propagation if no chain-breaking antioxidants are present (Scheme 2.1). However, in many biological situations chain-breaking antioxidants are present, for example, in LDL, and these will terminate the peroxyl radical and are consumed in the process. This will concomitandy increase the size of the peroxide pool in the membrane or lipoprotein. Such peroxides may be metabolized by the glutathione peroxidases in a cellular environment but are probably more stable in the plasma comjxutment. In the next section, the promotion of lipid peroxidation if the lipid peroxides encounter a transition metal will be considered. 

Thiols are also important protection against lipid peroxidation. Glutathione (7-Glu-Cys-Gly) is used by several glutathione-dependent enzymes such as free-radical reductase (converts vitamin E radical to vitamin E), glutathione peroxidase (reduces hydrogen peroxide and lipid hydroperoxides to water and to the lipid alcohol, respectively), and others. In addition, the thiol group of many proteins is essential for function. Oxidation of the thiol of calcium ATPases impairs function and leads to increased intracellular calcium. Thiol derivatives such as the ovothiols (l-methyl-4-mercaptohistidines) (Shapiro, 1991) have been explored as therapeutics. 

Lipid peroxidation activity. Solubilized green tea, administered orally to rats for 5 weeks, reduced lipid peroxidation products. The treatment produced increased activity of glutathione (GSFf) peroxidase and GSH reductase, increased content of reduced GSH, a marked decrease in lipid hydroperoxides and malondialdehyde in the liver, an increase in the concentration of vitamin A by about 40%. A minor change in the measured parameters was observed in the blood... 

Kaplan E. and Ansari K. (1984). Reduction of polyunsaturated fatty acid hydroperoxides by human brain glutathione peroxidase. Lipids 19 784-789. 

Glutathione peroxidases (GSH-Px) are enzymes catalyzing the reduction of hydrogen peroxide to water, and of lipid hydroperoxides to alcohols, with... 

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