Catechol-O-methyl transferase

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Catechol-O-methyltransferase
Identifiers
Symbol(s) COMT;
External IDs OMIM: 116790 MGI88470 Homologene30982
RNA expression pattern

PBB GE COMT 208818 s at tn.png

PBB GE COMT 208817 at tn.png

PBB GE COMT 213981 at tn.png

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 an enzyme first discovered by biochemist Julius Axelrod. COMT is the name given to the gene that codes for this enzyme. The O in the name stands for oxygen, not for ortho.

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.

L-DOPA, a precursor of catecholamines, is an important substrate of COMT. COMT inhibitors, like entacapone, save L-dopa from COMT and prolong the action of L-DOPA. Entacapone is a widely-used adjunct 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. 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.[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 norepinephrine and dopamine.[2] Tea may also help reduce the risk of breast cancer.[3] COMT inhibitors include tolcapone and entacapone.

See also

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". Biological Psychiatry 57 (10): 1117. doi:10.1016/j.biopsych.2005.01.026. ISSN 0006-3223. PMID 15866551.
  2. Blumenthal, Mark; Josef Brinckmann, Bernd Wollschlaeger (2003). The ABC Clinical Guide to Herbs. Haworth Press. ISBN 1588901572. 
  3. 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". Cancer Research 63 (21): 7526-7529. ISSN 0008-5472. PMID 14612555.

Further reading

  • Trendelenburg U (1991). "The interaction of transport mechanisms and intracellular enzymes in metabolizing systems.". J. Neural Transm. Suppl. 32: 3-18. PMID 2089098.
  • Tai CH, Wu RM (2002). "Catechol-O-methyltransferase and Parkinson's disease.". Acta Med. Okayama 56 (1): 1-6. PMID 11873938.
  • Zhu BT (2003). "On the mechanism of homocysteine pathophysiology and pathogenesis: a unifying hypothesis.". Histol. Histopathol. 17 (4): 1283-91. PMID 12371153.
  • Oroszi G, Goldman D (2005). "Alcoholism: genes and mechanisms.". Pharmacogenomics 5 (8): 1037-48. doi:10.1517/14622416.5.8.1037. PMID 15584875.
  • Fan JB, Zhang CS, Gu NF, et al. (2005). "Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis.". Biol. Psychiatry 57 (2): 139-44. doi:10.1016/j.biopsych.2004.10.018. PMID 15652872.
  • Tunbridge EM, Harrison PJ, Weinberger DR (2006). "Catechol-o-methyltransferase, cognition, and psychosis: Val158Met and beyond.". Biol. Psychiatry 60 (2): 141-51. doi:10.1016/j.biopsych.2005.10.024. PMID 16476412.
  • Diaz-Asper CM, Weinberger DR, Goldberg TE (2006). "Catechol-O-methyltransferase polymorphisms and some implications for cognitive therapeutics.". NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics 3 (1): 97-105. doi:10.1016/j.nurx.2005.12.010. PMID 16490416.
  • Craddock N, Owen MJ, O'Donovan MC (2006). "The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons.". Mol. Psychiatry 11 (5): 446-58. doi:10.1038/sj.mp.4001808. PMID 16505837.
  • Frank MJ, Moustafa AA, Haughey H, Curran T, Hutchison KE (2007). "Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning.". Proc Natl Acad Sci U S A 104 (41): 16311-6. doi:10.1073/pnas.0706111104. PMID 17913879.

External links

de:Catechol-O-Methyltransferase

it:Catecol-O-metiltrasferasi


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