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Catechol-O-methyl transferase

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Catechol-O-methyl transferase
Symbol(s): COMT
Locus: 22 q11 .21-q11.23
EC number 2.1.1.6
EntrezGene 1312
OMIM 116790
RefSeq NM_000754
UniProt P21964

Catechol-O-methyl transferase (COMT) (EC 2.1.1.6) is an enzyme first discovered by biochemist Julius Axelrod. COMT is the name given to the gene which codes for this enzyme. The O in the name stands for oxygen, not for ortho.

Function

Catechol-O-methyl transferase is involved in the breakdown of the catecholamine neurotransmitters, dopamine, epinephrine and norepinephrine. The enzyme introduces a methyl group to the catecholamine which is donated by S-adenosyl methionine (SAM). Any compound having a catechol structure, like catecholestrogens and catechol-containing flavonoids are substrates of COMT. L-dopa, a precursor of catecholamines, is an important substrate of COMT. COMT inhibitors, like entacapone saves L-dopa from COMT and prolongs the action of L-dopa. Entacapone is a widely used adjuct drug of L-dopa therapy. When given with an inhibitor of dopa decarboxylase (carbidopa or benserazide), L-dopa is optimally saved. This "triple therapy" is becoming a standard in the treatment of Parkinson's disease.

A functional single nucleotide polymorphism (a common normal variant) of the gene for catechol-O-methyl transferase has been shown to affect cognitive tasks broadly related to executive function, such as set shifting, response inhibition, abstract thought and the acquisition of rules or task structure. This polymorphism in the COMT gene results in the substitution of the amino acid valine for methionine. It has been shown that this valine variant catabolizes dopamine at up to four times the rate of its methionine counterpart, resulting in a significant reduction of synaptic dopamine following neurotransmitter release, ultimately reducing dopaminergic stimulation of the post-synaptic neuron. Consequently, neurons with valine-variant COMT show higher levels of activation during certain cognitive tasks, as they require higher levels of neuron firing to achieve the same level of post-synaptic stimulation.

The link between impairments in these sorts of cognitive tasks and the COMT gene is thought to be mediated by an effect on dopamine signalling in the frontal lobes.

Comparable effects on similar cognitive tasks, the frontal lobes and the neurotransmitter dopamine have also all been linked to schizophrenia. Unsurprisingly, an inherited variant of COMT is thought to be one of the genetic factors which may predispose someone to developing schizophrenia later in life, naturally or due to adolescent-onset cannabis use.[1]

COMT inhibitors

COMT inhibitors are found in green tea. Drinking green tea is, therefore, thought to provide a useful short-term boost to antidepressant medication by increasing the half life of extracellular noradrenaline and dopamine. [How to reference and link to summary or text] Tea may also help reduce the risk of breast cancer.[2]

COMT inhibitors include tropolone, entacapone.

Additional images

References

  1. Avshalom Caspi, Terrie E. Moffitt, Mary Cannon, Joseph McClay, Robin Murray, HonaLee Harrington, Alan Taylor, Louise Arseneault, Ben Williams, Antony Braithwaite, Richie Poulton, and Ian W. Craig (2005). Moderation of the Effect of Adolescent-Onset Cannabis Use on Adult Psychosis by a Functional Polymorphism in the catechol-O-Methyltransferase Gene:Longitudinal Evidence of a Gene X Environment Interaction. Society of Biological Psychiatry.
  2. Anna H. Wu2, Chiu-Chen Tseng, David Van Den Berg and Mimi C. Yu (2003). Tea Intake, COMT Genotype, and Breast Cancer in Asian-American Women.

See also


References & Bibliography

Key texts

Books

Papers

  • Akil M, Kolachana BS, Rothmond DA, Hyde TM, Weinberger DR, Kleinman JE. (2003). Catechol-O-methyltransferase genotype and dopamine regulation in the human brain. J Neurosci. Mar 15;23(6):2008-13.
  • Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, Egan MF, Kolachana B, Callicott JH, Weinberger DR. 2003 Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci U S A. Apr 25
  • Walker, H. A., Danielson, E., & Levitt, M. (1976). Catechol-O-methyltransferase activity in psychotic children: Journal of Autism & Childhood Schizophrenia Vol 6(3) Sep 1976, 263-268.

Additional material

Books

Papers



External links

  1. REDIRECT Template:One carbon transferasesCategory shizophrenia


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