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, iron, or nickel.
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 purified from the bovine erythrocytes: 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 and electrostatic 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 [1N0J], 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 forms of superoxide dismutase are present. 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.
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. It was once believed that ALS-causing mutations to SOD1 resulted in a destabilization of the protein, and that this destabilization was the universal basis for pathogenesis. However, in 2005, this notion was dispelled when it was shown that many pathogenic variants of SOD1 are not destabilized.
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]
