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Encyclopedia > Superoxide dismutase
Structure of the monomeric unit of human superoxide dismutase 2
superoxide dismutase 1, soluble
Identifiers
Symbol SOD1
Alt. Symbols ALS, ALS1
Entrez 6647
HUGO 11179
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 SOD2
Entrez 6648
HUGO 11180
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 SOD3
Entrez 6649
HUGO 11181
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. Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... Hugo is a masculine name. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The National Center for Biotechnology Information (NCBI) is part of the US National Library of Medicine (NLM), which is a branch of the US National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... Short and long arms Chromosome. ... Chromosome 21 is one of the 23 pairs of chromosomes in humans. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... Hugo is a masculine name. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The National Center for Biotechnology Information (NCBI) is part of the US National Library of Medicine (NLM), which is a branch of the US National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... Short and long arms Chromosome. ... Chromosome 6 is one of the 23 pairs of chromosomes in humans. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... Hugo is a masculine name. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The National Center for Biotechnology Information (NCBI) is part of the US National Library of Medicine (NLM), which is a branch of the US National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... Short and long arms Chromosome. ... Chromosome 4 is one of the 23 pairs of chromosomes in humans. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... Dismutation is a chemical reaction in which a single compound serves both as an oxidizing and a reducing agent. ... Lewis electron configuration of superoxide. ... General Name, Symbol, Number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ... Hydrogen peroxide (H2O2) is a very pale blue liquid which appears colourless in a dilute solution, slightly more viscous than water. ... Space-filling model of the antioxidant metabolite glutathione. ... Binomial name Lactobacillus plantarum (Orla-Jensen 1919) Bergey 1923 Lactobacillus plantarum is a widespread member of the genus Lactobacillus, commonly found in sauerkraut, pickles, brined olives, korean kimchi, nigerian ogi, sourdugh and other fermented plant material and also in some cheeses and fermented sausages. ... Species L. acidophilus L. brevis L. delbrueckii subsp. ...

Contents

Reaction

The SOD-catalysed dismutation of superoxide may be written with the following half-reactions : Dismutation is a chemical reaction in which a single compound serves both as an oxidizing and a reducing agent. ... Lewis electron configuration of superoxide. ...

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

where M = Cu (n=1) ; Mn (n=2) ; Fe (n=2) ; Ni (n=2). CU may stand for: Cervecerias Unidas, SA, NYSE ticker symbol Champaign-Urbana Metropolitan Area Christian Union, a political party in the Netherlands College University, an animated Internet-based comedy series Control unit credit union CU (Powerline), a HVDC-powerline in the USA Cuba, ISO 3166, FIPS Pub 10-4 and... General Name, Symbol, Number manganese, Mn, 25 Chemical series transition metals Group, Period, Block 7, 4, d Appearance silvery metallic Standard atomic weight 54. ... General Name, Symbol, Number iron, Fe, 26 Chemical series transition metals Group, Period, Block 8, 4, d Appearance lustrous metallic with a grayish tinge Standard atomic weight 55. ... General Name, Symbol, Number nickel, Ni, 28 Chemical series transition metals Group, Period, Block 10, 4, d Appearance lustrous, metallic and silvery with a gold tinge Standard atomic weight 58. ...


In this reaction the oxidation state of the metal cation oscillates between n and n+1. In chemistry, the oxidation state is an indicator of the degree of oxidation of an atom in a chemical compound. ...


Types

General

Several common forms of SOD exist: they are proteins cofactored with copper and zinc, or manganese, iron, or nickel. Copper proteins are proteins that contain one or more copper ions as prosthetic groups. ... General Name, Symbol, Number zinc, Zn, 30 Chemical series transition metals Group, Period, Block 12, 4, d Appearance bluish pale gray Standard atomic weight 65. ... General Name, Symbol, Number manganese, Mn, 25 Chemical series transition metals Group, Period, Block 7, 4, d Appearance silvery metallic Standard atomic weight 54. ... General Name, Symbol, Number iron, Fe, 26 Chemical series transition metals Group, Period, Block 8, 4, d Appearance lustrous metallic with a grayish tinge Standard atomic weight 55. ... General Name, Symbol, Number nickel, Ni, 28 Chemical series transition metals Group, Period, Block 10, 4, d Appearance lustrous, metallic and silvery with a gold tinge Standard atomic weight 58. ...

  • 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 depending on the Mn oxidation state (respectively II and III). The cytosol (cf. ... Kingdoms Animalia - Animals Fungi Plantae - Plants Protista Alternative Phylogeny Unikonta    Opisthokonta    Amoebozoa Bikonta    Apusozoa    Cabozoa       Rhizaria       Excavata    Corticata       Archaeplastida       Chromalveolata Animals, plants, fungi, and protists are eukaryotes (IPA: ), organisms with a complex cell or cells, where the genetic material is organized into a membrane-bound nucleus or nuclei. ... General Name, Symbol, Number copper, Cu, 29 Chemical series transition metals Group, Period, Block 11, 4, d Appearance metallic pinkish red Standard atomic weight 63. ... General Name, Symbol, Number zinc, Zn, 30 Chemical series transition metals Group, Period, Block 12, 4, d Appearance bluish pale gray Standard atomic weight 65. ... The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. ... Histidine is one of the 20 most common natural amino acids present in proteins. ... In cell biology, a mitochondrion is an organelle found in the cells of most eukaryotes. ... Phyla Actinobacteria Aquificae Chlamydiae Bacteroidetes/Chlorobi Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Lentisphaerae Nitrospirae Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Verrucomicrobia Bacteria (singular: bacterium) are unicellular microorganisms. ... Binomial name Escherichia coli T. Escherich, 1885 Escherichia coli (usually abbreviated to E. coli) is one of the main species of bacteria that live in the lower intestines of warm-blooded animals (including birds and mammals) and are necessary for the proper digestion of food. ... General Name, Symbol, Number manganese, Mn, 25 Chemical series transition metals Group, Period, Block 7, 4, d Appearance silvery metallic Standard atomic weight 54. ... The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. ... Histidine is one of the 20 most common natural amino acids present in proteins. ... Aspartic acid, also known as aspartate, the name of its anion, is one of the 20 natural proteinogenic amino acids which are the building blocks of proteins. ... This prefix in chemical nomenclature indicates the presence of a hydroxyl functional group (-OH). ... In chemistry, a ligand is an atom, ion, or molecule (see also: functional group) that generally donates one or more of its electrons through a coordinate covalent bond to, or shares its electrons through a covalent bond with, one or more central atoms or ions (these ligands act as a...

  • 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
Structure of the active site of human superoxide dismutase 2

General Name, Symbol, Number iron, Fe, 26 Chemical series transition metals Group, Period, Block 8, 4, d Appearance lustrous metallic with a grayish tinge Standard atomic weight 55. ... The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. ... Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ...

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). It has been suggested that Cytoplast be merged into this article or section. ... Electron micrograph of a mitochondrion showing its mitochondrial matrix and membranes In cell biology, a mitochondrion (plural mitochondria) (from Greek μιτος or mitos, thread + χονδριον or khondrion, granule) is a membrane-enclosed organelle, found in most eukaryotic cells. ... In cell biology, molecular biology and related fields, the word extracellular means outside the cell. It is used in contrast to intracellular (inside the cell). ... Sucrose, or common table sugar, is composed of glucose and fructose. ... General Name, Symbol, Number manganese, Mn, 25 Chemical series transition metals Group, Period, Block 7, 4, d Appearance silvery metallic Standard atomic weight 54. ... For a non-technical introduction to the topic, see Introduction to Genetics. ...


A microtiter plate assay for SOD is available[1].


Biochemistry

The superoxide anion radical (O2-) spontaneously dismutes to O2 and H2O2 or hydrogen peroxide 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. Turnover number (also termed kcat) is defined as the maximum number of moles of substrate that an enzyme can convert to product per catalytic site per unit time and can be calulated as follows: kcat = Vmax/[E]T. ...


Physiology

Superoxide is one of the main reactive oxygen species 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[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]. Reactive oxygen species (ROS) include oxygen ions, free radicals and peroxides both inorganic and organic. ... Oxidative stress is a medical term for damage to animal or plant cells (and thereby the organs and tissues composed of those cells) caused by reactive oxygen species, which include (but are not limited to) superoxide, singlet oxygen, peroxynitrite or hydrogen peroxide. ...


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. Amyotrophic lateral sclerosis (ALS, sometimes called Lou Gehrigs disease, Maladie de Charcot or motor neurone disease) is a progressive, fatal neurodegenerative disease caused by the degeneration of motor neurons. ... Motor neuron disease (MND) is a term used to cover a number of illnesses of the motor neurone; amyotrophic lateral sclerosis (ALS), progressive muscular atrophy (PMA), spinal muscular atrophy (SMA), progressive bulbar palsy (PBP), and primary lateral sclerosis (PLS) are all forms of MND. MND is the term used internationally... Hepatocellular carcinoma (HCC, also called hepatoma) is a primary malignancy (cancer) of the liver. ...


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 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 [1], possible through reversion of myofibroblasts back to fibroblasts Histological section through testicular parenchyma of a boar. ... A fibroblast is a cell that makes the structural fibers and ground substance of connective tissue. ...


References

  1. ^ 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. 
  2. ^ a b Image:Free_text.png Li, et al., Y. (1995). "Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase.". Nat. Genet. 11: 376-381. 
  3. ^ a b Image:Free_text.png Elchuri, et al., S. (2005). "CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life.". Oncogene 24: 367-380. 
  4. ^ Image:Free_text.png Muller, et al., F. L. (2006). "Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy.". Free Radic. Biol. Med 40: 1993-2004. 
  5. ^ Image:Free_text.png Sentman, et al., M. L. (2006). "Phenotypes of mice lacking extracellular superoxide dismutase and copper- and zinc-containing superoxide dismutase". J. Biol. Chem. 281: 6904-6909. DOI:10.1074/jbc.M510764200. 
  6. ^ Image:Free_text.png Groner, Y. et al. (1994). "Cell damage by excess CuZnSOD and Down's syndrome.". Biomed Pharmacother. 48: 231-40. PMID 7999984. 
  7. ^ Image:Free_text.png Campana, F. (2004). "Topical superoxide dismutase reduces post-irradiation breast cancer fibrosis" (available free). J. Cell. Mol. Med. 8 (1): 109–116. PMID 15090266. 

Image File history File links Free_text. ... Image File history File links Free_text. ... Image File history File links Free_text. ... Image File history File links Free_text. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Image File history File links Free_text. ... Image File history File links Free_text. ...

See also

Catalase (human erythrocyte catalase: PDB 1DGF, EC 1. ... Glutathione Peroxidase 1 A peroxidase (eg. ...

External links


  Results from FactBites:
 
anti age, free radicals, superoxide dismutase, antioxidants : frequently asked questions (338 words)
The superoxide dismutase is a natural enzyme of the organism, able to neutralise superoxide anion very quickly.
Thus, superoxide anion is naturally knocked down slowly and partially, what gives it time to react with other molecules, causing considerable damage.
The SOD, superoxide dismutase, is a major antioxidant enzyme, the anti-rust enzyme of the organism’s cells.
Superoxide Dismutase : by Ray Sahelian, M.D. (918 words)
Superoxide dismutase has been found in almost all organisms living in the presence of oxygen, including some anaerobic bacteria, supporting the notion that superoxide is a key and general component of oxidative stress.
Extra cellular superoxide dismutase (EC-SOD) catalyzes the dismutation of superoxide radical to hydrogen peroxide and oxygen in the interstitial spaces of tissues and in extracellular fluids (plasma, lymph, and synovial fluid).
In the mid 1990s, the linkage between mutations in the gene coding for the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) and the neurodegenerative disease known as familial amyotrophic lateral sclerosis was established.
  More results at FactBites »


 

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