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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.

FunctionEdit

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 Edit

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 imagesEdit

References Edit

  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.
  • Bassett, A. S., Caluseriu, O., Weksberg, R., Young, D. A., & Chow, E. W. C. (2007). Catechol-o-methyl transferase and expression of schizophrenia in 73 adults with 22q11 deletion syndrome: Biological Psychiatry Vol 61(10) May 2007, 1135-1140.
  • Brooks, D. J. (2004). Safety and tolerability of COMT inhibitors: Neurology Vol 62(1,Suppl1) Jan 2004, S39-S46.
  • Burdick, K. E., Funke, B., Goldberg, J. F., Bates, J. A., Jaeger, J., Kucherlapati, R., et al. (2007). COMT genotype increases risk for bipolar I disorder and influences neurocognitive performance: Bipolar Disorders Vol 9(4) Jun 2007, 370-376.
  • Cavallini, M. C., Di Bella, D., Catalano, M., & Bellodi, L. (2000). An association study between 5-HTTLPR polymorphism, COMT polymorphism, and Tourette's syndrome: Psychiatry Research Vol 97(2-3) Dec 2000, 93-100.
  • Chan, R. C. K., Chen, R. Y. L., Chen, E. Y. H., Hui, T. C. K., Cheung, E. F. C., Cheung, H. K., et al. (2005). The differential clinical and neurocognitive profiles of COMT SNP rs165599 genotypes in schizophrenia: Journal of the International Neuropsychological Society Vol 11(2) Mar 2005, 202-204.
  • Craddock, N., Owen, M. J., & O'Donovan, M. C. (2006). The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: Evidence and lessons: Molecular Psychiatry Vol 11(5) May 2006, 446-458.
  • De Luca, V., Tharmalingam, S., Muller, D. J., Wong, G., de Bartolomeis, A., & Kennedy, J. L. (2006). Gene-gene interaction between MAOA and COMT in suicidal behavior: Analysis in schizophrenia: Brain Research Vol 1097(1) Jun 2006, 26-30.
  • Domschke, K., Freitag, C. M., Kuhlenbaumer, G., Schirmacher, A., Sand, P., Nyhuis, P., et al. (2004). Association of the functional V158M catechol-O-methyl-transferase polymorphism with panic disorder in women: International Journal of Neuropsychopharmacology Vol 7(2) Jun 2004, 183-188.
  • Dronjak, S., & Gavrilovic, L. (2006). Effects of stress on catecholamine stores in central and peripheral tissues of long-term socially isolated rats: Brazilian Journal of Medical and Biological Research Vol 39(6) Jun 2006, 785-790.
  • Farmer, A., Elkin, A., & McGuffin, P. (2007). The genetics of bipolar affective disorder: Current Opinion in Psychiatry Vol 20(1) Jan 2007, 8-12.
  • Galderisi, S., Maj, M., Kirkpatrick, B., Piccardi, P., Mucci, A., Invernizzi, G., et al. (2005). COMT Valsuperscript 1-sup-5-sup-8 Met and BDNF Csuperscript 2-sup-7-sup-0T polymorphisms in schizophrenia: A case-control study: Schizophrenia Research Vol 73(1) Feb 2005, 27-30.
  • Guo, S., Chen, D. F., Zhou, D. F., Sun, H. Q., Wu, G. Y., Haile, C. N., et al. (2007). Association of functional catechol O-methyl transferase (COMT) Val108Met polymorphism with smoking severity and age of smoking initiation in Chinese male smokers: Psychopharmacology Vol 190(4) Mar 2007, 449-456.
  • Ho, B. C., Wassink, T. H., O'Leary, D. S., Sheffield, V. C., & Andreasen, N. C. (2005). Catechol-O-methyl transferase Valsuperscript 1-sup-5-sup-8Met gene polymorphism in schizophrenia: Working memory, frontal lobe MRI morphology and frontal cerebral blood flow: Molecular Psychiatry Vol 10(3) Mar 2005, 229.
  • Jabbi, M., Korf, J., Kema, I. P., Hartman, C., van der Pompe, G., Minderaa, R. B., et al. (2007). Convergent genetic modulation of the endocrine stress response involves polymorphic variations of 5-HTT, COMT and MAOA: Molecular Psychiatry Vol 12(5) May 2007, 483-490.
  • Joo, E.-J., Jeong, S.-H., Ahn, Y.-M., Lee, K.-Y., Yoon, S. C., Kim, E.-J., et al. (2005). No association found between 158 Val/Met polymorphism of the COMT gene and schizophrenia with minor physical anomalies: Psychiatry Research Vol 136(2-3) Sep 2005, 83-91.
  • Karayiorgou, M., Gogos, J. A., Galke, B. L., Wolyniec, P. S., Nestadt, G., Antonarakis, S. E., et al. (1998). Identification of sequence variants and analysis of the role of the catechol-O-methyl-transferase gene in schizophrenia susceptibility: Biological Psychiatry Vol 43(6) Mar 1998, 425-431.
  • Li, T., Sham, P. C., Vallada, H., Xie, T., & et al. (1996). Preferential transmission of the high activity allele of COMT in schizophrenia: Psychiatric Genetics Vol 6(3) Fal 1996, 131-133.
  • Niehaus, D. J. H., Kinnear, C. J., Corfield, V. A., du Toit, P. L., van Kradenburg, J., Moolman-Smook, J. C., et al. (2001). Association between a catechol-o-methyltransferase polymorphism and obsessive-compulsive disorder in the Afrikaner population: Journal of Affective Disorders Vol 65(1) Jun 2001, 61-65.
  • Ohnishi, T., Hashimoto, R., Mori, T., Nemoto, K., Moriguchi, Y., Iida, H., et al. (2006). The association between the Val158Met polymorphism of the catechol-O-methyl transferase gene and morphological abnormalities of the brain in chronic schizophrenia: Brain: A Journal of Neurology Vol 129(2) Feb 2006, 399-410.
  • Olanow, C. W., & Stocchi, F. (2004). COMT inhibitors in Parkinson's disease: Can they prevent and/or reverse levodopa-induced motor complications? : Neurology Vol 62(1,Suppl1) Jan 2004, S72-S81.
  • Owen, M. J., Williams, N. M., & O'Donovan, M. C. (2004). The molecular genetics of schizophrenia: New findings promise new insights: Molecular Psychiatry Vol 9(1) Jan 2004, 14-27.
  • Palmatier, M. A., Pakstis, A. J., Speed, W., Paschou, P., Goldman, D., Odunsi, A., et al. (2004). COMT haplotypes suggest P2 promoter region relevance for schizophrenia: Molecular Psychiatry Vol 9(9) Sep 2004, 859-870.
  • Poewe, W. (2004). The role of COMT inhibition in the treatment of Parkinson's disease: Neurology Vol 62(1,Suppl1) Jan 2004, S31-S38.
  • Reyes-Gibby, C. C., Shete, S., Rakvag, T., Bhat, S. V., Skorpen, F., Bruera, E., et al. (2007). Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene: Pain Vol 130(1-2) Jul 2007, 25-30.
  • Saadat, M. (2005). Correction of estimation of allelic frequency in Galderisi et al. study: Schizophrenia Research Vol 78(2-3) Oct 2005, 351.
  • Schott, B. H., Seidenbecher, C. I., Fenker, D. B., Lauer, C. J., Bunzeck, N., Bernstein, H.-G., et al. (2006). The Dopaminergic Midbrain Participates in Human Episodic Memory Formation: Evidence from Genetic Imaging: Journal of Neuroscience Vol 26(5) Feb 2006, 1407-1417.
  • Serretti, A., Cusin, C., Cristina, S., Lorenzi, C., Lilli, R., Lattuada, E., et al. (2003). Multicentre Italian family-based association study on tyrosine hydroxylase, catechol-O-methyl transferase and Wolfram syndrome 1 polymorphisms in mood disorders: Psychiatric Genetics Vol 13(2) Jun 2003, 121-126.
  • Sliwerska, E., Meng, F., Speed, T. P., Jones, E. G., Bunney, W. E., Akil, H., et al. (2007). SNPs on Chips: The Hidden Genetic Code in Expression Arrays: Biological Psychiatry Vol 61(1) Jan 2007, 13-16.
  • Stefanis, N. C., Henquet, C., Avramopoulos, D., Smyrnis, N., Evdokimidis, I., Myin-Germeys, I., et al. (2007). COMT Valsuperscript 1-sup-5-sup-8Met moderation of stress-induced psychosis: Psychological Medicine Vol 37(11) Nov 2007, 1651-1656.
  • Suzuki, A., Nakamura, K., Sekine, Y., Minabe, Y., Takei, N., Suzuki, K., et al. (2006). An association study between catechol-O-methyl transferase gene polymorphism and methamphetamine psychotic disorder: Psychiatric Genetics Vol 16(4) Aug 2006, 133-138.
  • Williams, H. J., Owen, M. J., & O'Donovan, M. C. (2007). Is COMT a susceptibility gene for schizophrenia? : Schizophrenia Bulletin Vol 33(3) May 2007, 635-641.
  • Xu, H., Kellendonk, C. B., Simpson, E. H., Keilp, J. G., Bruder, G. E., Polan, H. J., et al. (2007). DRD2 C957T polymorphism interacts with the COMT Val158Met polymorphism in human working memory ability: Schizophrenia Research Vol 90(1-3) Feb 2007, 104-107.
  • Zintzaras, E., & Sakelaridis, N. (2007). Is 472G/A catechol-O-methyl-transferase gene polymorphism related to panic disorder? : Psychiatric Genetics Vol 17(5) Oct 2007, 267-273.

See alsoEdit


References & BibliographyEdit

Key textsEdit

BooksEdit

PapersEdit

  • 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 materialEdit

BooksEdit

PapersEdit



External linksEdit

  1. REDIRECT Template:One carbon transferasesCategory shizophrenia


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