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The enzyme superoxide dismutase (SOD, EC 188.8.131.52), catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide. As such it is an important antioxidant defense in nearly all cells exposed to oxygen. One of the exceedingly rare exceptions is Lactobacillus plantarum and related lactobacilli.
A typical reaction of an SOD protein containing copper (and zinc) looks like this:
- Cu+2-SOD + O2- → Cu+1-SOD + O2
- Cu+1-SOD + O2- + 2H+ → Cu+2-SOD + H2O2.
In this reaction the oxidation state of the copper changes between +1 and +2.
- The cytosols of virtually all eukaryotic cells contain an SOD enzyme with copper and zinc (Cu-Zn-SOD). (For example, Cu-Zn-SOD available commercially is normally that found in the bovine erythrocyte: PDB 1SXA, EC 184.108.40.206). The Cu-Zn enzyme is a homodimer of molecular weight 32,500. The two subunits are joined by a disulfide bond.
- Chicken liver (and nearly all other) mitochondria, and many bacteria (such as E. coli) contain a form with manganese (Mn-SOD). (For example, the Mn-SOD found in a human mitochondrion: PDB 1ABM, EC 220.127.116.11).
- E. coli and many other bacteria also contain a form of the enzyme with iron (Fe-SOD); some bacteria contain Fe-SOD, others Mn-SOD, and some contain both. (For the E. coli Fe-SOD: PDB 1ISA, EC 18.104.22.168).
In humans, three types are recognised. SOD1 is located in the cytoplasm, SOD2 in the mitochondria and SOD3 is extracellular. The former is a dimer (consists of two units), while the others are tetramers (four subunits). SOD1 and SOD3 contain copper and zinc, while SOD2 has manganese in its reactive centre. The genes are located on chromosomes 21, 6 and 4, respectively (21q22.1, 6q25.3 and 4p15.3-p15.1).
The superoxide anion radical (O2-) spontaneously dismutes to O2 and H2O2 quite rapidly. However, SOD has the fastest turnover number (reaction rate with its substrate) of any known enzyme. In fact, its rate is diffusion-limited. Thus under real-world intracellular conditions SOD greatly reduces the ambient level of the dangerous superoxide radical.
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.
Role in disease
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