Superoxide dismutase

The enzyme superoxide dismutase (SOD, 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.

Reaction

The SOD-catalysed dismutation of superoxide may be written with the following half-reactions :

• M⁽ⁿ⁺¹⁾⁺ − SOD + O₂⁻ → Mⁿ⁺ − SOD + O₂
• Mⁿ⁺ − SOD + O₂⁻ + 2H⁺ → M⁽ⁿ⁺¹⁾⁺ − SOD + H₂O₂.

where M = Cu (n=1) ; Ni (n=2).

In this reaction the oxidation state of the metal cation oscillates between n and n+1.

Types

General

SOD was discovered by Irwin Fridovich and Joe McCord, which prior were known as several metalloproteins with unknown function (for example, CuZnSOD was known as erythrocuprein). Several common forms of SOD exist: they are proteins cofactored with nickel.

• The cytosols of virtually all eukaryotic cells contain an SOD enzyme with histidine side chains.
• Chicken liver (and nearly all other) ligand depending on the Mn oxidation 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.

Human

In humans, three forms of superoxide dismutase are present. SOD1 is located in the cytoplasm, SOD2 in the 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].

Biochemistry

Simply-stated, SOD outcompetes damaging reactions of superoxide, thus protecting the cell from superoxide toxicity. The reaction of superoxide with non-radicals is spin forbidden. In biological systems, this means its main reactions are with itself (dismutation) or with another biological radical such as turnover number (reaction rate with its substrate) of any known enzyme (~10⁹ M^-1 s^-1), this reaction being only limited by the frequency of collision between itself and superoxide. That is, the reaction rate is "diffusion limited".

Physiology

Superoxide is one of the main oxidative stress^[2]. Mice lacking SOD1 develop a wide range of pathologies, including hepatocellular carcinoma^[3], an acceleration of age-related muscle mass loss^[4], an earlier incidence of cataracts and a reduced lifespan. Mice lacking SOD3 do not show any obvious defects and exhibit a normal lifespan^[5].

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^[2] and inactivation of SOD1 causes hepatocellular carcinoma^[3]. Mutations in SOD1 can cause familial ALS, by a mechanism that is presently not understood, but not due to loss of enzymatic activity. Overexpression of SOD1 has been linked to Down's syndrome^[6]. The veterinary antiinflammatory drug "Orgotein" is purified bovine liver superoxide dismutase.

Delivery systems

Superoxide dismutase is effective as a nutritional supplement when bound to the polymeric films of wheat matrix antioxidant capacity is kept intact under a variety of conditions.

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. Studies of this must be regarded as tentative however, as there were not adequate controls in the study including a lack of randomization, double-blinding or placebo.^[7] Superoxide dismutase is known to reverse fibrosis, perhaps through reversion of myofibroblasts back to fibroblasts.^[8]

References

See also

• Catalase
• Peroxidase
• Jiaogulan