Welcome to the MedLibrary.org Wikipedia Supplement on COMT -- Please Click to Return to Front Page

Catechol-O-methyltransferase
Cartoon diagram of human COMT in complex with 3,5-dinitrocatechol (dark blue) and S-adenosyl methionine (yellow). From PDB 3BWM.
Identifiers
Symbols	COMT;
External IDs	OMIM: 116790 MGI: 88470 HomoloGene: 30982
Gene ontology Molecular function: • magnesium ion binding • protein binding • O-methyltransferase activity • catechol O-methyltransferase activity • transferase activity Cellular component: • soluble fraction • microsome • membrane • integral to membrane Biological process: • catecholamine metabolic process • dopamine catabolic process
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	1312	12846
Ensembl	ENSG00000093010	ENSMUSG00000000326
Uniprot	P21964	Q91XH4
Refseq	NM_000754 (mRNA) NP_000745 (protein)	NM_007744 (mRNA) NP_031770 (protein)
Location	Chr 22: 18.31 - 18.34 Mb	Chr 16: 18.32 - 18.33 Mb
Pubmed search	[1]	[2]

Catechol-O-methyl transferase (COMT; EC 2.1.1.6) is one of several enzymes that degrade catecholamines such as dopamine, epinephrine, and norepinephrine. As the regulation of catecholamines is impaired in a number of medical conditions, several pharmaceutical drugs target COMT to alter its activity and therefore the availability of catecholamines. COMT was first discovered by the biochemist Julius Axelrod.

Contents 1 Function 2 Genetics 2.1 The val158met polymorphism 3 Nomenclature 4 COMT inhibitors 5 See also 6 Additional images 7 References 8 Further reading 9 External links

Function

Catechol-O-methyl transferase is involved in the inactivation 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). COMT is an intracellular enzyme located in the postsynaptic neuron. Any compound having a catechol structure, like catecholestrogens and catechol-containing flavonoids, are substrates of COMT.

Levodopa, a precursor of catecholamines, is an important substrate of COMT. COMT inhibitors, like entacapone, save levodopa from COMT and prolong the action of levodopa. Entacapone is a widely-used adjunct drug of levodopa therapy. When given with an inhibitor of dopa decarboxylase (carbidopa or benserazide), levodopa is optimally saved. This "triple therapy" is becoming a standard in the treatment of Parkinson's disease.

Genetics

The COMT protein is coded by the gene COMT. The gene is associated with allelic variants. The most well-studied is Val158Met (rs737865). Others are rs737865 and rs165599 that have been studied, e.g., for association with personality traits.^[1]

The val158met polymorphism

SNP: Catechol-O-methyl transferase
Name(s)	Val158Met, Val108/158Met, G1947A
Gene	COMT
Chromosome	22
Region	Exon 3
External databases
Ensembl	Human SNPView
dbSNP	4680
HapMap	4680
SNPedia	4680
HgenetInfoDB	4680
AlzGene	Meta-analysis	Overview
SzGene	Meta-analysis	Overview

Val158Met (rs4680), 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.^{citation needed} This polymorphism in the COMT gene results in the substitution of the amino acid valine for methionine at codon 158, thus the name Val158Met for the polymorphism. 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. As a consequence, 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 signaling in the frontal lobes.

Comparable effects on similar cognitive tasks, the frontal lobes, and the neurotransmitter dopamine have also all been linked to schizophrenia. It is not surprising, then, that an inherited variant of COMT is thought to be one of the genetic factors that may predispose someone to developing schizophrenia later in life, naturally or due to adolescent-onset cannabis use.^[2]

Nomenclature

COMT is the name given to the gene that codes for this enzyme. The O in the name stands for oxygen, not for ortho.

COMT inhibitors

COMT inhibitors include tolcapone and entacapone, which are commonly used in the treatment of Parkinson disease.

See also

• Dopamine
• Schizophrenia
• Methyltransferase

Additional images

References

1. ^ Murray B. Stein, Margaret Daniele Fallin, Nicholas J. Schork & Joel Gelernter (November 2005). "COMT polymorphisms and anxiety-related personality traits". Neuropsychopharmacology 30 (11): 2092–2092. doi:10.1038/sj.npp.1300787. PMID 15956988. 
2. ^ 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". Biological Psychiatry 57 (10): 1117. doi:10.1016/j.biopsych.2005.01.026. ISSN 0006-3223. PMID 15866551. 

Further reading

External links

• MeSH Catechol+O-Methyltransferase

v • d • e Transferase: one carbon transferases (EC 2.1) 2.1.1 - Methyltransferases N-methyltransferase: Histamine N-methyltransferase - Phenylethanolamine N-methyltransferase - Tryptamine N-methyltransferase - Phosphatidylethanolamine N-methyltransferase O-methyltransferase: 5-hydroxyindole-O-methyltransferase/Acetylserotonin O-methyltransferase - Catechol-O-methyl transferase homocysteine methyltransferase: Betaine-homocysteine methyltransferase - Homocysteine methyltransferase - 5-Methyltetrahydrofolate-homocysteine methyltransferase Other: Phosphatidyl ethanolamine methyltransferase - DNMT3B - Histone methyltransferase - Thymidylate synthase - DNA methyltransferase 2.1.2 - Hydroxy methyl-, Formyl- and Related Transferases Serine hydroxymethyltransferase - Phosphoribosylglycinamide formyltransferase - Inosine monophosphate synthase - Glutamate formimidoyltransferase - Aminomethyltransferase 2.1.3 - Carboxy- and Carbamoyl transferases Ornithine transcarbamylase 2.1.4 - Amidino transferases Arginine:glycine amidinotransferase

v • d • e Metabolism: amino acid metabolism - neurotransmitter enzymes histidine→histamine anabolism: Histidine decarboxylase catabolism: Histamine N-methyltransferase - Amine oxidase tyrosine→dopamine→epinephrine anabolism: Tyrosine hydroxylase - Aromatic L-amino acid decarboxylase - Dopamine beta hydroxylase - Phenylethanolamine N-methyltransferase catabolism: Catechol-O-methyl transferase - Monoamine oxidase glutamate→GABA anabolism: Glutamate decarboxylase catabolism: 4-aminobutyrate aminotransferase - 4-aminobutyrate transaminase tryptophan→serotonin→melatonin Tryptophan hydroxylase - Aromatic L-amino acid decarboxylase - Acetylserotonin O-methyltransferase arginine→NO Nitric oxide synthase (NOS1, NOS2A, NOS3) choline→Acetylcholine anabolism: Choline acetyltransferase catabolism: Cholinesterase (Acetylcholinesterase, Butyrylcholinesterase) see also intermediates

Wikipedia content modification information:

• This page was last modified on 4 September 2008, at 11:50.

Wikipedia Authorship and Review

Wikipedia content provided here is not reviewed directly by MedLibrary.org. Wikipedia content is authored by an open community of volunteers and is not produced by or in any way affiliated with MedLibrary.org.

Wikipedia Usage Guidelines

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article on "COMT".

The URL for this specific entry is:

• http://medlibrary.org/medwiki/COMT

All Wikipedia text is available under the terms of the GNU Free Documentation License. (See Copyrights for details). Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc.