Superoxide dismutase

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For other senses of the term SOD/Sod, see Sod (disambiguation).

Structure of the monomeric unit of human superoxide dismutase 2

superoxide dismutase 1, soluble
Identifiers
Symbol(s)	SOD1 ALS, ALS1
Entrez	6647
OMIM	147450
RefSeq	NM_000454
UniProt	P00441
Other data
EC number	1.15.1.1
Locus	Chr. 21 q22.1

superoxide dismutase 2, mitochondrial
Identifiers
Symbol(s)	SOD2
Entrez	6648
OMIM	147460
RefSeq	NM_000636
UniProt	P04179
Other data
EC number	1.15.1.1
Locus	Chr. 6 q25

superoxide dismutase 3, extracellular
Identifiers
Symbol(s)	SOD3
Entrez	6649
OMIM	185490
RefSeq	NM_003102
UniProt	P08294
Other data
EC number	1.15.1.1
Locus	Chr. 4 pter-q21

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, which use a different mechanism.

1 Reaction
2 Types
- 2.1 General
- 2.2 Human
3 Biochemistry
4 Physiology
5 Role in disease
6 Cosmetic uses
7 References
8 See also
9 External links

[edit] Reaction

A typical reaction of an SOD protein containing copper (and zinc) looks like this:

Cu²⁺ − SOD + O₂⁻ → Cu⁺ − SOD + O₂
Cu⁺ − SOD + O₂⁻ + 2H⁺ → Cu²⁺ − SOD + H₂O₂.

In this reaction the oxidation state of the copper changes between +1 and +2. Similar reactions can be written for Fe and Mn which oscillate between the +2 and +3 oxidation states.

[edit] Types

[edit] 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. The ligands of copper and zinc are histidine side chains.
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). The ligands of the manganese ions are 3 histidine side chains,

an aspartate side chain and a water molecule or hydroxy ligand dependig on the Mn oxydation state (respectively II and III).

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). The active sites of Mn and Fe superoxide dismutases contain the same type of amino acids side chains.

Structure of the active site of human superoxide dismutase 2

[edit] 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].

[edit] Biochemistry

The superoxide anion radical (O₂^-) spontaneously dismutes to O₂ and H₂O₂ quite rapidly (~10⁵ M^-1 s^-1 at pH 7). Nevertheless, superoxide reacts even faster with certain targets such as NO, which can form peroxynitrite. However, SOD has the fastest turnover number (reaction rate with its substrate) of any known enzyme (~10⁹ M^-1 s^-1), the reaction being only limited by the frequency of collision between itself and superoxide (the reaction rate is said to be diffusion limited). Thus SOD outcompetes damaging reactions of superoxide protecting the cell from superoxide toxicity.

[edit] Physiology

Superoxide is one of the main pro-oxidants in the cell and as such, SOD serves a key antioxidant role. The physiological importance of SODs is illustrated by the severe pathologies evident in mice genetically engineered to lack these enzymes. Mice lacking SOD2 die several days after birth, amidst massive oxidative stress. Mice lacking SOD1 develop a wide range of pathologies, including hepatocellular carcinoma, an acceleration of age-related muscle mass loss, an earlier incidence of cataracts and a reduced lifespan. Mice lacking SOD3 do not show any obvious defects and exhibit a normal lifespan.

[edit] 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. 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.

[edit] 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. These studies must be regarded as tenatative however, as there were not adequate controls in the study including a lack of randomization, double-blinding or placebo. ^[2]

[edit] 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. PubMed Free text - PDF 333kB