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.

Catechol-O-methyltransferase (COMT) genotypes are associated with varying soluble, but not membrane-bound COMT protein in the human prefrontal cortex.

Abstract: Catechol-O-methyltransferase (COMT) is an enzyme that catalyses the O-methylation, and thereby the inactivation, of catechol-containing molecules In humans, it has been suggested that COMT modulates cognitive ability, possibly by regulating degradation of dopamine in the prefrontal cortex Hence, it is significant that two COMT SNPs, rs4680 (c472 G > A, pVal158Met) and rs4818 (c408 C > G), have been associated with cognitive ability in humans We have shown these SNPs to be associated with levels of muscarinic M1 receptor mRNA in human cortex, which is significant as that receptor also regulates cognitive ability We decided to determine if COMT genotype was associated with varying levels of COMT protein, as this could be a mechanism by which COMT genotype could be associated with changes in muscarinic M1 receptor mRNA levels Hence, we measured COMT levels in prefrontal cortex obtained postmortem from 199 subjects, some of whom had a history of schizophrenia, major depressive disorders or bipolar disorders Our data show, independent of diagnostic status, that genotype at rs4680 and rs4818, but not at rs737865 and rs165599, is associated with differing levels of soluble COMT (S-COMT), but not membrane-bound COMT (MB-COMT) These findings suggest that the association between COMT polymorphisms and cognitive functioning could be, at least in part, due to their association with varying levels of S-COMT This is important as, unlike MB-COMT, the substrates targeted by S-COMT are likely to be intra-cellular rather than, like dopamine, located mainly in the synaptic vesicles or the extra-cellular space

Catechol-O-methyltransferase enzyme: cofactor S-adenosyl-L-methionine and related mechanisms.

Abstract: Long-term daily repeated intake of traditional levodopa (L-dopa)/dopa decarboxylase inhibitor (DDI) formulations increases the homocysteine synthesis in plasma of Parkinson's disease patients with unforeseen consequences, like an augmented vulnerability for onset of concomitant non-motor symptoms. Homocysteine decrease may therefore be a future therapeutic challenge, which may be achieved by supplementation with certain vitamins or by combination of a catechol-O-methyltransferase (COMT) inhibitor with L-dopa/DDI administration. Monitoring of plasma homocysteine concentration may also serve as biomarker for the detoxification potential of endogenous, exogenous, and environmental toxins. These substrates may also accumulate in the nervous system, since homocysteine formation is associated with O-methylation which has a broad detoxification potential.

Activity of catechol-o-methyltransferase in brain regions and adrenal gland during the oestrus cycle.

Abstract: The activity of the enzyme catechol-O-methyltransferase (COMT) during four different phases of the oestrus cycle were determined. Brain and hypothalamus had highest level of COMT activity during oestrus phase, while at pro-oestrus it was at its lowest level. COMT activity in the adrenal gland was also modified during the four phases with the maximum level at met-oestrus and the minimum at pro-oestrus phase. The results provide evidence to show that COMT in the brain, hypothalamus and the adrenals is markedly affected by changes in physiological status of the female rats and its evolution in brain is different from adrenal gland during the oestrus cycle. The variations in the activity of COMT may be the consequence of modified endocrine activity which takes place naturally during oestrus cycle.