General Background All organisms living in an aerobic environment are exposed to reactive oxygen species (ROS) that are formed through metabolic processes and various environmental stresses . ROS are unstable and extremely reactive, the chemical reactivity induces lipid peroxidation and protein oxidation/degradation . The effect of ROS on cell fate depends on the level at which they are present. There are three main types of ROS: : SUPER-OXIDE arises from the mitochondrial respiratory chain and is constitutively present in cells; : HYDROGEN-PEROXIDE arises from dismutation of : OXYGEN-MOLECULE or the action of oxidase enzymes; and highly reactive : CPD-12377 produced from the decomposition of : HYDROGEN-PEROXIDE, modifies purine and pyrimidine bases and causes DNA strand breaks . ROS levels in moderation have a normal physiological role in health, controlling inflammatory and immune responses and participating in signal transduction. However, unbalanced levels of ROS are related to many disorders, including cardiovascular disease, Alzheimer's disease, pulmonary diseases, diabetes, aging and cancer. Most aerobic organisms have developed defense systems to scavenge oxidative radicals and combat oxidative stress, in the form of enzymes that can detoxify ROS. Since ROS can be found in any compartment of the eukaryotic cell, organisms have developed small gene families encoding specific enzymes that operate in the various cell compartments . About this Pathway The superoxide dismutases (SODs) represent the first line of defense against ROS, converting : SUPER-OXIDE radicals to : HYDROGEN-PEROXIDE and water . SODs are differentiated with regard to their metal cofactor. There are manganese-dependent and copper/zinc-dependent SODs, which differ not only in their metal cofactor but also in their subcellular location. Human : CPLX66-541 is found in the mitochondrion and is structurally very similar to bacterial FeSODs. The : CPLX66-540 operates in the cytosol and the : CPLX66-542 operates outside the cell. Both are structurally different from : CPLX66-541 because of the different electrical properties of copper in comparison to manganese, which results in a major structural change in the protein . Hydrogen peroxide can be converted to water and/or oxygen by the glutathione peroxidases or catalase . Catalases are found in the peroxisome. Through the glutathione peroxidases, this pathway is connected to : PWY-4081. Hydrogen peroxide can also spontaneously form the : CPD-12377. The hydroxyl radical cannot be eliminated by an enzymatic reaction and is neutralized by the action of antioxidants such as : ASCORBATE

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CAT , GPX1 , GPX2 , GPX3 , GPX7 , SOD1 , SOD2 , SOD3 , GPX6 , GPX8 ,