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.

The role of catechol-O-methyl transferase Val(108/158)Met polymorphism (rs4680) in the effect of green tea on resting energy expenditure and fat oxidation: a pilot study.

Abstract: Introduction: Green tea(GT) is able to increase energy expenditure(EE) and fat oxidation(FATox) via inhibition of catechol-O-methyl transferase(COMT) by catechins. However, this does not always appear unanimously because of large inter-individual variability. This may be explained by different alleles of the functional COMT Val108/158Met polymorphism that are associated with COMT enzyme activity; high-activity enzyme, COMTH(Val/Val genotype), and low-activity COMT L (Met/Met genotype). Methods: Fourteen Caucasian subjects (BMI: 22.2 +/- 2.3 kg/m(2), age: 21.4 +/- 2.2 years) of whom 7 with the COMTH-genotype and 7 with the COMTL-genotype were included in a randomized, cross-over study in which EE and substrate oxidation were measured with a ventilated-hood system after decaffeinated GT and placebo(PL) consumption. Results: At baseline, EE, RQ, FATox and carbohydrate oxidation(CHOox) did not differ between groups. Significant interactions were observed between COMT genotypes and treatment for RQ, FATox and CHOox (p Conclusion: Subjects carrying the COMTH genotype increased energy expenditure and fat-oxidation upon ingestion of green tea catechins vs, placebo, whereas COMTL genotype carriers reacted similarly to GT and PL ingestion. The differences in responses were due to the different responses on PL ingestion, but similar responses to GT ingestion, pointing to different mechanisms. The different alleles of the functional COMT Val108/158Met polymorphism appear to play a role in the inter-individual variability for EE and FATox after GT treatment.

Catechol O-methyltransferase: characterization of the protein, its gene, and the preclinical pharmacology of COMT inhibitors.

Abstract: Publisher Summary Catechol O-methyltransferase (COMT) is an enzyme that catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to one of the phenolic group of the catechol substrate in the presence of Mg2+ and following a sequential ordered mechanism. High COMT activity is found in the liver, kidney, and gut wall. A single COMT gene codes two separate enzymes, the soluble(S-COMT) and membrane-bound (MB-COMT) forms. S-COMT contains 221 amino acids. MB-COMT has an additional amino terminal extension of 43 (rat) or 50 (human) amino acids. Synthesis of recombinant S-COMT in E. coli and MB-COMT in the insect cells using vectors has helped in clarifying the biochemistry, physiology, and pharmacology of COMT. MB-COMT is partially responsible of the termination of dopaminergic and noradrenergic synaptic neurotransmission. S-COMT is a high-capacity enzyme responsible for the elimination of biologically active or toxic, particularly exogenous catechols and some hydroxylated metabolites. Accordingly, MB-COMT is a dominating isoenzyme in the human brain. Second-generation COMT inhibitors are potent, selective, and orally active. The current COMT inhibitors have been divided into three groups—mainly peripherally acting nitrocatechol-type compounds, broad-spectrum nitrocatechols having activity both in the periphery and the brain; and atypical compounds and pyridine, some of which are not COMT inhibitors in vitro but may instead inhibit catechol O-methylation by some other mechanism. COMT inhibitors improve the brain entry of L-dopa and decrease 3-OMD formation in the peripheral tissues. COMT inhibitors should also decrease fluctuations of the dopamine formation. A summary of some preclinical evidence supporting the suggested use is given in this chapter. Noradrenaline and dopamine deficiency in the synaptic cleft depicts depression. The remedy of this deficit by the use of tricyclic uptake inhibitors and monoamine oxidase inhibitors has become an established therapy for depression. The COMT inhibitors reaching the brain would decrease the metabolism of noradrenaline and dopamine.

Bimodal administration of entacapone in Parkinson's disease patients improves motor control.

Abstract: Catechol-O-methyl transferase (COMT) inhibition by entacapone enhances levodopa absorption and reduces 'off' time in Parkinson's disease (PD). We hypothesized that the administration of entacapone in a bimodal fashion (two doses 1 h apart) would enhance levodopa absorption and improve the motor symptoms of PD. Patients with PD (n = 17) were given immediate (IR)- or controlled (CR)-release levodopa each with either one or two doses of entacapone. Bimodal entacapone produced a significant increase in IR and CR levodopa half-life, 'area under the curve' (AUC), and C(max) with levodopa CR. For both IR and CR levodopa, bimodal entacapone resulted in a significant improvement in the Unified Parkinson's Disease Rating Scale part III (motor). Bimodal entacapone increased COMT inhibition, improved the pharmacokinetics of levodopa and improved motor scores for 6 to 8 h. Bimodal use of entacapone may be useful in selected patients to improve motor control and implies that controlled release COMT inhibition would be beneficial in PD patients.

Magnified effects of the COMT gene on white-matter microstructure in very old age.

Abstract: Genetic factors may partly account for between-person differences in brain integrity in old age. Evidence from human and animal studies suggests that the dopaminergic system is implicated in the modulation of white-matter integrity. We investigated whether a genetic variation in the Catechol-O-Methyltransferase (COMT) Val158Met polymorphism, which influences dopamine availability in prefrontal cortex, contributes to interindividual differences in white-matter microstructure, as measured with diffusion-tensor imaging. In a sample of older adults from a population-based study (60-87 years; n = 238), we found that the COMT polymorphism affects white-matter microstructure, indexed by fractional anisotropy and mean diffusivity, of several white-matter tracts in the oldest age group (81-87 years), although there were no reliable associations between COMT and white-matter microstructure in the two younger age groups (60-66 and 72-78 years). These findings extend previous observations of magnified genetic effects on cognition in old age to white-matter integrity.

Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson's disease.

Abstract: Objectives: Cognitive decline is common in Parkinson's disease (PD), but the underlying mechanisms for this complication are incompletely understood. Genotypes affecting dopamine transmission may b ...