Glutathione peroxidase antioxidant defense

Finally, metabolism and inactivation of Cd-induced ROS by cells and tissues can also be perceived as indirect processes that contribute to Cd detoxification. The cellular antioxidative defense mechanisms responsible for ROS scavenging have been thoroughly reviewed [474,489]. They include antioxidative enzymes (e.g., superoxide dismutases, catalases, glutathione peroxidases, antioxidative metabolites (GSH, ascorbic acid, vitamin E) and the enzymes involved in their regeneration (thioredioxins, glutaredoxins, glutathione reductases). 

Oxidative stress generally describes a condition in which cellular antioxidant defenses are inadequate to completely detoxify the free radicals being generated, because of excessive production of ROS, loss of antioxidant defenses or, typically, both [23]. This condition may occur locally, as antioxidant defenses may become overwhelmed at certain subcellular locations while remaining intact overall, and selectively with regard to radical species, as antioxidant defenses are radical-specific - for example SOD for superoxide and catalase or glutathione peroxidase for H202. 

To reduce the injurious effect of oxidative stress, cells are equipped with two major antioxidant defense systems. The first concerns numerous enzymes, which catalyze ROS degradation, such as superoxide dismutase (SOD), catalase or glutathione peroxidase (GPx) ... 

Although inorganic selenium does not have antioxidant properties, selenium has an important role in cellular antioxidant defenses as a necessary component of selenoproteins. Selenium is incorporated into selenoproteins as selenocysteine. The glutathione (GSH) peroxidases are the best-characterized selenoproteins, although other circulating selenoproteins also have antioxidant functions. 

Although glutathione is specifically decreased in kwashiorkor, blood levels of selenium-dependent glutathione peroxidase (a scavenger of peroxides) and vitamins A, C, and E (all members of the antioxidant machinery) are lower in both kwashiorkor and marasmus (Ashour et al., 1999). Why then are marasmic children, also deficient in some antioxidants, spared the oxidative stress Does a weakened antioxidant defense manifest as a serious threat only in the presence of pro-oxidant activities of the type encountered in kwashiorkor What is a possible trigger for the increase in free radicals, and how might this account for some of the phenotypic alterations in kwashiorkor ... 

Gerdin E, Tyden O, Eriksson UJ. The development of antioxidant enzymatic defense in the perinatal rat lung. Activities of superoxide dismutase, glutathione peroxidase and catalase. Pediatr Res 19 (1985) 687-691. 

Recent studies have shown that cyanide also inhibits the antioxidant defense enzymes (such as catalase, superoxide dismutase, and glutathione peroxidase) and stimulates neurotransmitter release. These effects of cyanide may also contribute to its acute toxicity. The prolonged energy deficit and the consequent loss of ionic homeostasis, which may result in activation of calcium signaling cascade and eventually cell injury, contribute to cyanide toxicity resulting from subacute exposure or in the postintoxication sequela. 

The intercepting defenses scavenge the generated free radicals. As mentioned previously, superoxide dismutase and a-tocopherol are good examples of enzyme and nonenzyme scavengers, respectively. Some dietary minerals are essential for the function of antioxidant enzymes (e.g., the various isoforms of superoxide dismutase use copper and zinc or manganese as cofactors, whereas an isoform of glutathione peroxidase uses selenium). 

The four important enzymatic components of the cellular antioxidant defense system. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide (02-) to peroxide. Catalase reduces peroxide to H20. GSH peroxidase also detoxifies peroxide by reducing it to H20. GSH reductase re-reduces the oxidized glutathione (GSSG) to GSH. The NADPH required for the reduction of GSSG to GSH is primarily supplied by the oxidation of glucose via the pentose phosphate pathway. (Based on Mottet, N.K., Ed. Environmental Pathology. Oxford University Press, New York, 1985.)... 

Superoxide dismutase and catalase are remarkably efficient, performing their reactions at or near the diffusion-limited rate (p. 221). Glutathione peroxidase also plays a role in scavenging HjO.) (p. 587). Other cellular defenses against oxidative damage include the antioxidant vitamins, vitamins... 

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