| Superoxide dismutases (SOD) are a large and ubiquitous family of metalloenzymes that exist primarily to convert superoxide into hydrogen peroxide and water. This metal-containing antioxidant enzyme that reduces potentially harmful free radicals of oxygen formed during normal metabolic cell processes to oxygen and hydrogen peroxide. Hydrogen peroxide is always formed when
superoxide is formed by way of the dismutation reaction. Most oxidases in the body directly reduce oxygen to hydrogen peroxide. Oxidative metabolism in respiring cells generates highly reactive superoxide radicals which cause cellular damage. The presence of SOD has been shown to help protect many types of cells from the free radical damage that is important in aging, senescence, and ischemic tissue damage. SOD also helps protect cells from DNA damage, lipid peroxidation, ionizing radiation damage, protein denaturation, and many other forms of progressive cell degradation.
Several common forms of SOD exist: they are proteins cofactored with copper and zinc, or manganese, or iron. Copper/zinc SODs are typically found in the nuclei and cytosols of eukaryotic cells, iron SODs are typically found in prokaryotes, and manganese SODs are typically localized in the mitochondrial matrices of both eukaryotic and prokaryotic cells. Manganese superoxide dismutase and iron superoxide dismutase from some organisms (e.g. Escherichia coli) exhibit almost absolute metal specificity, while other enzymes, such as `cambialistic' superoxide dismutase from Propionibacterium shermanii, are active with either metal. Manganese superoxide dismutase and iron superoxide dismutase occur as homodimers or homotetramers. Manganese superoxide dismutase and iron superoxide dismutase are unequally distributed throughout the kingdoms of living organisms and are located in different cellular compartments. In particular, iron superoxide dismutase is found in facultative aerobes, in the thylakoid membranes of cyanobacteria and the chloroplasts of higher plants, and in mitochondria of higher plants, fungi and animals.
The activity of the superoxide dismutases make them excellent candidates for therapeutic agents to counteract the toxic effects of the superoxide and other oxygen radicals. Pharmacologically, superoxide dismutase can serve as a medicine for treatment of inflammation caused by autoimmune diseases, and, recently, by use of superoxide dismutase, there have been attempts to develop medicines for the treatment of arthritis deformans and chronic rheumatism and for treatment of harmful side effects caused by radio therapy. Manganese superoxide dismutase (MnSOD) is a very important antioxidant enzyme that catalyzes the conversion of superoxide radicals to hydrogen peroxide and molecular oxygen in the mitochondria. Alterations in MnSOD levels have been associated with a number of neurodegenerative diseases, including Parkinson’s disease, Duchenne muscular dystrophy, Charcot-Marie-Tooth disease, and Kennedy-Alter-Sung syndrome. Many different types of tumors have been demonstrated to have low MnSOD activity. |
