Glutathione reactive oxygen species

Glutathione-peroxidase (GSH-Pxase) is an enzyme found in erythroqrtes and other tissues that has an essential selenocysteine residue involved in the catalytic decomposition of reactive oxygen species. In the erythrocyte, hydrogen peroxide is the principle reactive oxygen species available. 

Fig. 2 Possible mechanisms by which nanoparticles cause toxicity inside cells. GSH glutathione, GSSG glutathione disulfide, MDA malondialdehyde, NFkB nuclear factor kappa B, Nrf2 nuclear factor-erythroid 2-related factor 2, ROS reactive oxygen species...

The antioxidant system in humans is a complex network composed by several enzymatic and nonenzymatic antioxidants. In addition to being an antioxidant, lycopene also exerts indirect antioxidant properties by inducing the production of cellular enzymes such as superoxide dismutase, glutathione S-transferase, and quinone reductase that also protect cells from reactive oxygen species and other electrophilic molecules (Goo and others 2007). 

Protection against cell damage due to oxidative stress is provided, amongst others, by glutathione (GSH), a cellular tripeptide with a thiol function in a cysteine residue. GSH is deprotonated to GS, which is a scavenger for electrophilic compounds and is reduced to GS SG in defense of reactive oxygen species [28]. 

All aerobic organisms contain substances that help prevent injury mediated by free radicals, and these include antioxidants such as a-tocopherol and the enzymes superoxide dismutase and glutathione peroxidase. When the protective effect of the antioxidants is overwhelmed by the production of reactive oxygen species, the intracellular milieu becomes oxidative, leading to a state known as oxidative stress (Halliwell and Gutteridge, 1999). Thus the balance between the generated free radicals and the efficiency of the protective antioxidant system determines the extent of cellular damage. 

Maintenance of a supply of reduced glutathione to protect against reactive oxygen species (ROS)... 

As well as the formation of radicals, oxidative stress may also contribute to the toxicity of electrophilic metabolites. This may result from depletion by electrophiles of the glutathione pool, one of the major defenses against damage by reactive oxygen species. 

Reactive oxygen species react with and denature cellular components, particularly hemoglobin, leading to premature RBC death and hemolysis unless they are reduced by glutathione, which is dependent on NADPH for its regeneration. 

Galati, G. et al., Glutathione-dependent generation of reactive oxygen species by the peroxidase-catalysed redox cycling of flavonoids, Chem. Res. Toxicol., 12, 521, 1999. 

Figure 7.46 The metabolism and toxicity of primaquine. Two metabolites, (1) 6-methoxy-8-hydroxyl am in oqui noline and (2) 5-hydroxyprimaquine, are known to be capable of causing oxidative stress and producing ROS. ROS and the metabolites can be removed by GSH, but when this is depleted, they may damage the red cell cytoskeleton and hemoglobin. Abbreviations ROS, reactive oxygen species GSH, glutathione.

Activation of the promutagen/carcinogen benzo[a]pyrene by reactive oxygen species/liver P-450 (S-9) fraction and reaction of benzo[a]pyrene epoxydiol with DNA. GSH = glutathione, DNA = deoxyribonucleic acids, X = a general nucleophile not specifically explicated. 

Reactive oxygen species produced in mitochondria are inactivated by a set of protective enzymes, including superoxide dismutase and glutathione peroxidase. 

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