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Catechol-O-methyl transferase

About: Catechol-O-methyl transferase is a research topic. Over the lifetime, 1646 publications have been published within this topic receiving 87360 citations.


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Journal ArticleDOI
TL;DR: The genetic variant of the COMT rs4680 single nucleotide polymorphism is associated with variability in opioid consumption in postoperative nephrectomy patients and may prove useful in predicting emesis medication use postoperatively.
Abstract: BACKGROUND:Previous studies have associated the catechol-O-methyltransferase (COMT) enzyme rs4680 polymorphism with opioid consumption in the treatment of chronic cancer pain. In this study, we evaluated the association between COMT rs4680 and rs4818 polymorphisms and opioid consumption in the acute

49 citations

Journal ArticleDOI
TL;DR: According to the mechanistic understanding developed here, a novel dietary strategy is proposed that is specifically tailored toward lowering the risk of human PD, which includes eating a nutritionally-balanced diet that contains adequate amounts of fruits and vegetables, along with adequate dietary supplementation of S-adenosyl-L-methionine, vitamins C, B6, B12, and folate.
Abstract: In this article, a particular emphasis has been placed on the conceptual development and understanding of the unique pathogenic changes that are indigenous to the striatal dopaminergic neurons as an important etiological factor in human Parkinson's disease (PD) as well as on the understanding of their clinical implications. Specifically, I have discussed the etiological roles of central nervous system dopamine oxidation in PD, along with a critical review of the available evidence in support of the proposed hypotheses. The chemically-reactive dopamine quinone/semiquinone intermediates are known to be highly neurotoxic and potentially genotoxic. There is considerable evidence for the suggestion that the long-term use of levodopa accelerates the progression of PD. In comparison, centrally-acting non-catechol dopamine receptor agonists would be an excellent alternative to levodopa for the treatment of PD (particularly for late-stage PD) because these agents would not undergo redox cycling to cause oxidative neuronal damage. Catechol-O-methyltransferase (COMT)-mediated methylation metabolism of catecholamine neurotransmitters is a crucial first-line detoxification pathway, and its role in the causation and prevention of PD is also discussed. On the basis of the modulation of COMT-mediated methylation of catecholamines, it is mechanistically explained that hyperhomocysteinemia would be a pathogenic factor in PD whereas vitamins B6, B12, and folate would be a protective factor. Lastly, according to the mechanistic understanding developed here, a novel dietary strategy is proposed that is specifically tailored toward lowering the risk of human PD, which includes eating a nutritionally-balanced diet that contains adequate (but not excessive) amounts of fruits and vegetables, along with adequate dietary supplementation of S-adenosyl-L-methionine, vitamins C, B6, B12, and folate. It is believed that these conceptual developments would also aid in our better understanding of other age-related neurodegenerative disorders, such as Alzheimer's and Huntington's diseases.

48 citations

Journal ArticleDOI
TL;DR: The results confirmed the associations between Met allele and aggressive behaviour or violent suicide attempts in various psychiatric diagnoses, and suggested that Met allele of the COMT Val108/158 Met might be used as an independent biomarker of suicidal behaviour across different psychopathologies.
Abstract: Alcohol dependence is frequently associated with aggressive and suicidal behaviour. Genetic factors contribute to both behaviours. Candidate genes, related to suicide and aggression, include genes involved in serotonin, norepinephrine and dopamine pathways. The enzyme catechol-O-methyl transferase (COMT) degrades dopamine, epinephrine and norepinephrine. The functional polymorphism (COMT Val108/158Met) affects COMT activity, with the valine (Val) variant associated with higher and the methionine (Met) variant with lower COMT activity. This polymorphism is associated with aggressive and suicidal behaviour, but the literature data on this relationship is contradictory and inconsistent. The hypothesis of this study was that Met allele carriers with alcohol dependence will have a higher frequency of suicide attempts compared to other genotypes. Participants were 312 male and 81 female medication-free patients with alcohol dependence and 487 male and 122 female unrelated, non-suicidal medication-free Caucasian healthy subjects. Our results showed significant (χ2 test with standardized residuals) differences in the frequencies of COMT variants in all alcoholics, alcoholics with different comorbid diagnoses, and in male but not in female alcoholics, with or without suicide attempts. Male alcoholic suicide attempters, compared to male non-attempters, had the higher frequency of Met/Met genotype or Met allele, and significantly (Kruskal-Wallis ANOVA on ranks and Mann-Whitney test) higher aggression and depression scores. These results confirmed the associations between Met allele and aggressive behaviour or violent suicide attempts in various psychiatric diagnoses, and suggested that Met allele of the COMT Val108/158 Met might be used as an independent biomarker of suicidal behaviour across different psychopathologies. Language: en

48 citations

Journal ArticleDOI
TL;DR: The biochemical characteristics of soluble catechol‐O‐methyltransferase (COMT) activity in rat erythrocytes were compared with the properties of the soluble enzyme in rat liver, heart, and brain to measure COMT by a procedure that avoided artifacts of some other assay procedures including inhibition of the enzyme by endogenous calcium.
Abstract: The biochemical characteristics of soluble catechol-O-methyltransferase (COMT) activity in rat erythrocytes were compared with the properties of the soluble enzyme in rat liver, heart, and brain. COMT was measured by a procedure that avoided artifacts of some other assay procedures including inhibition of the enzyme by endogenous calcium. After the removal of calcium from the reaction mixture the apparent Michaelis-Menten constants for the two cosubstrates of the COMT reaction, S-adenosyl-1-methionine (SAM) and 3,4-dihydroxybenzoic acid (DBA), were similar in tissue preparations of rat liver, brain, heart and blood. The apparent Km values for the four tissues ranged from 5.7 to 6.7 x 10(-6) M and from 0.9-1.4 x 10(-4) M for SAM and DBA, respectively. The optimal pH and the optimal concentration of magnesium for the assay of red blood cell COMT were also similar to those for the enzyme in the three other rat tissues. After the removal of endogenous calcium, COMT activity in all four tissues was inhibited by the addition of calcium, and the [CaCl2] necessary to inhibit the enzyme activity 50% was 3-5 x 10(-4) M in all cases. The relative activities of COMT in the rat heart, brain, erythrocyte, and liver when expressed per g tissue or per ml of packed red blood cells were 1 to 1.15 to 1.58 to 140, respectively.

48 citations

Journal ArticleDOI
TL;DR: Soeiro‐de‐Souza MG, Machado‐Vieira R, Soares Bio D, Do Prado CM, Moreno RA COMT polymorphisms as predictors of cognitive dysfunction during manic and mixed episodes in bipolar I disorder.
Abstract: Soeiro-de-Souza MG, Machado-Vieira R, Soares Bio D, Do Prado CM, Moreno RA. COMT polymorphisms as predictors of cognitive dysfunction during manic and mixed episodes in bipolar I disorder. Bipolar Disord 2012: 14: 554–564. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: The dopaminergic system plays an important role in the prefrontal cortex (PFC) and is believed to mediate cognitive dysfunction (CD) in bipolar disorder (BD). The enzyme catechol-O-methyltransferase (COMT) is involved in the catabolism of dopamine in the PFC, and an association between COMT single nucleotide polymorphisms (SNPs) and BD has been reported. COMT SNPs have also been associated with executive and working memory performance in healthy subjects, patients with schizophrenia, and euthymic BD patients. The objective of this study was to investigate the association between COMT SNPs and acute CD during BD mood episodes. Methods: Seventy-two symptomatic, medication-free subjects with bipolar I disorder (BD-I) and 76 healthy controls were evaluated using neuropsychological tests, and genotyped for COMT SNPs rs4680 and rs165599. Results: Patients undergoing mania and mixed episodes carrying the COMT allele G had better performance on executive function, memory, verbal fluency, and intelligence tests. Moreover, an interaction was detected between the COMT allele G and the Young Mania Rating Scale in BD CD. Conclusions: Allele G from COMT SNPs rs4680 and rs165599 may represent reliable state-dependent predictors of global CD during manic and mixed episodes in BD. Further studies in larger samples are necessary to confirm these findings.

48 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202338
202265
202129
202032
201931
201834