The enzyme superoxide dismutase (SOD, EC 1.15.1.1), 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.
Structure of superoxide dismutase
Reaction
A typical reaction of an SOD protein containing copper (and zinc) looks like this:
- Cu2+-SOD + O2- → Cu1+-SOD + O2
- Cu1+-SOD + O2- + 2H+ → Cu2+-SOD + H2O2.
In this reaction the oxidation state of the copper changes between +1 and +2.
Types
General
Several common forms of SOD exist: they are proteins cofactored with copper and zinc, or manganese, or iron.
- 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 1.15.1.1). The Cu-Zn enzyme is a homodimer of molecular weight 32,500. The two subunits are joined primarily by hydrophobic interactions.
- 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 1.15.1.1).
- 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 1.15.1.1).
Human
In humans, three types are recognised. SOD1 is located in the cytoplasm, SOD2 in the mitochondria and SOD3 is extracellular. The first 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).
A microtiter plate assay for SOD is available[1].
Physiology
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
Mutations in the first SOD enzyme (SOD1) have been linked to familial amyotrophic lateral sclerosis (ALS, a form of motor neuron disease). The other two types have not been linked to any human diseases, however, in mice inactivation of SOD2 causes perinatal lethality and inactivation of SOD1 causes hepatocellular carcinoma.
Cosmetic uses
SOD is used in cosmetic products to reduce free radical damage to skin, for example to reduce fibrosis following radiation for breast cancer.[2]
References
- a A.V. Peskin, C.C. Winterbourn (2000). "A microtiter plate assay for superoxide dismutase using a water-soluble tetrazolium salt (WST-1)". Clinica Chimica Acta 293: 157–166.
- a
Campana, F. (2004). "Topical superoxide dismutase reduces post-irradiation breast cancer fibrosis". J. Cell. Mol. Med. 8 (1): 109–116. PMID 15090266 Free text - PDF 333kB
See also
External links
