Catechol- O- methyltransferase

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Catechol- O- methyltransferase
Catechol-O-methyltransferase
Ribbon model of human S-COMT in complex with 3,5-dinitrocatechol (blue) and S-adenosylmethionine (yellow)

Existing structural data : 3BWM , 3BWY

Properties of human protein
Mass / length primary structure 271 amino acids, 30,037 Da
Cofactor magnesium
Isoforms soluble, membrane-bound
Identifier
Gene name COMT
External IDs
Enzyme classification
EC, category 2.1.1.6 ,  methyltransferase
Response type Transfer of a methyl group
Substrate S-adenosyl methionine + catecholamine
Products S-adenosyl-L-homocysteine ​​+ guaiacol derivative
Occurrence
Homology family COMT
Parent taxon Creature
Exceptions | - Orthologue (human)
Entrez 1312
Ensemble ENSG00000093010
UniProt P21964
Refseq (mRNA) NM_000754.3
Refseq (protein) NP_000745.1
PubMed search 1312

Catechol O methyl transferase (gene: COMT ) is the one enzyme that different catecholamines , including natural neurotransmitters and neuroactive drugs, O-methylated and thus inactivated and the reduction supplies. It is part of the catecholamine breakdown and the metabolism of foreign substances . COMT is found in all living things and especially in the brain , in the liver and placenta , as well as in lymphocytes and erythrocytes expressed . There are two isoforms of COMT in humans : MB-COMT is membrane-bound and S-COMT (which lacks the first 50 amino acids) can move freely.

COMT was discovered by the US biochemist Julius Axelrod .

function

Dopamine degradation with the participation of catechol- O- methyltransferase

COMT deactivates noradrenaline , adrenaline and dopamine , particularly in the sympathetic nerve endings . These neurotransmitters are inactivated by the transfer of a methyl group from the S- adenosylmethionine (SAM) to a phenolic hydroxyl group by the catechol- O- methyltransferase, which is followed by the oxidative deamination by the monoamine oxidase (MAO).

COMT also metabolizes various drugs , also through methylation , such as the compounds levodopa and dopamine used in the treatment of Parkinson's disease . In order to switch off this deactivation, COMT inhibitors were developed.

pathology

COMT polymorphisms , i.e. the appearance of gene variants, are associated with a number of psychological changes such as anxiety disorders and schizophrenia , but also specifically eating disorders and obesity. These relationships, as well as the role of COMT in the processing of pain, are currently being researched. The results on schizophrenia are inconsistent.

Environmental toxins, but also the soy ingredients daidzein and genistein , can block the COMT and thus contribute to an accumulation of degradation products with the following damage to the organism.

In a retrospective study it could be shown that patients with a reduced COMT activity suffer more often a shock during bypass operations and have a higher risk of death during the operation.

Preeclampsia is associated with COMT deficiency.

Individual evidence

  1. ↑ Ross JR, Riley J, Taegetmeyer AB, et al : Genetic variation and response to morphine in cancer patients: catechol-O-methyltransferase and multidrug resistance-1 gene polymorphisms are associated with central side effects . In: Cancer . 112, No. 6, March 2008, pp. 1390-403. doi : 10.1002 / cncr.23292 . PMID 18257092 .
  2. ^ Bassett AS, Chow EW: Schizophrenia and 22q11.2 deletion syndrome . In: Curr Psychiatry Rep . 10, No. 2, April 2008, pp. 148-57. PMID 18474208 .
  3. ↑ Silberschmidt AL, Sponheim SR: Personality in relation to genetic liability for schizophrenia and bipolar disorder: differential associations with the COMT Val 108/158 Met polymorphism . In: Schizophr. Res. . 100, No. 1-3, March 2008, pp. 316-24. doi : 10.1016 / j.schres.2007.12.467 . PMID 18201871 .
  4. ↑ Sanders AR, Duan J, Levinson DF, et al : No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics . In: Am J Psychiatry . 165, No. 4, April 2008, pp. 497-506. doi : 10.1176 / appi.ajp.2007.07101573 . PMID 18198266 .
  5. ↑ Haase-Fielitz A, Haase M, Bellomo R, et al .: Decreased Catecholamine Degradation Associates with Shock and Kidney Injury after Cardiac Surgery , In: J Am Soc Nephrol . 2009, 20: 1393-1403. PMID 19406978
  6. ↑ UniProt P21964
  7. ↑ Ho PW, Garner CE, Ho JW, et al : Estrogenic phenol and catechol metabolites of PCBs modulate catechol-O-methyltransferase expression via the estrogen receptor: potential contribution to cancer risk . In: Curr. Drug metab. . 9, No. 4, May 2008, pp. 304-9. PMID 18473748 .
  8. ↑ Ho PW, Chu AC, Kwok KH, et al : Effects of plasticisers and related compounds on the expression of the soluble form of catechol-O-methyltransferase in MCF-7 cells . In: Curr. Drug metab. . 9, No. 4, May 2008, pp. 276-9. PMID 18473745 .
  9. ↑ Lehmann L, Jiang L, Wagner J: Soy isoflavones decrease the catechol-O-methyltransferase-mediated inactivation of 4-hydroxyestradiol in cultured MCF-7 cells . In: Carcinogenesis . 29, No. 2, February 2008, pp. 363-70. doi : 10.1093 / carcin / bgm235 . PMID 18192686 .
  10. ↑ Kanasaki K, Palmsten K, Sugimoto H, et al : Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia . In: Nature . 453, No. 7198, June 2008, pp. 1117-21. doi : 10.1038 / nature06951 . PMID 18469803 .