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COMT
Catechol-O-methyltransferase (COMT: EC 2.1.1.6) is an enzyme that in the presence of magnesium (Mg2+) catalyses the transference of a methyl group from Sadenosyl-L-methionine (SAM) to a catechol substrate with O-methylated catechol and S-adenosyl-L-homocysteine (SAH) as reaction products. As a ubiquitous enzyme COMT has been found in most studied organisms across phylogenetic levels, including yeasts, plants, insects, fish, amphibians, birds and all studied mammals. In humans, besides its role in CA catabolism COMT has been implicated in the inactivation of catecholoestrogen (CE), catechol-containing xenobiotics, such as catechins and bioflavonoids, and indole intermediates from melanin metabolism. COMT is strictly intracellular with two known isoforms, one soluble in the cytoplasm (soluble COMT: S-COMT) and one associated to membranes (membrane bound COMT: MB-COMT).
Due to the presence of a CArG box in the promoter, COMT has been identified as a transcriptional target for myocardin-related transcription factors (MRTFs), with the activation occurring through histone acetyltransferase p300 recruitment by megakaryoblastic leukemia 1 (MKL1). Possible targets for p53 and for the transcription factors AP-2, NF-IL6, HNF-4, Ets-1 and NF-D have also been described. Several CpG islets have been found in the 50 upstream region and their methylation was shown to silence MB-COMT expression. COMT seems to act as a physiological barrier at the blood–brain barrier, gastrointestinal tract and placenta. The enzyme also regulates levels of dopamine (DA) and norepinephrine (NE) in several cerebral regions, inactivates postsynaptic CA and protects dopaminergic neurons from the free radicals generated by the oxidative metabolism of DA.
References
1.Mamidi S, et al. Immunobiology. 2017 Jan;222(1):45-54.
1.Bastos P,et al. Rev Physiol Biochem Pharmacol. 2017;173:1-39.
Due to the presence of a CArG box in the promoter, COMT has been identified as a transcriptional target for myocardin-related transcription factors (MRTFs), with the activation occurring through histone acetyltransferase p300 recruitment by megakaryoblastic leukemia 1 (MKL1). Possible targets for p53 and for the transcription factors AP-2, NF-IL6, HNF-4, Ets-1 and NF-D have also been described. Several CpG islets have been found in the 50 upstream region and their methylation was shown to silence MB-COMT expression. COMT seems to act as a physiological barrier at the blood–brain barrier, gastrointestinal tract and placenta. The enzyme also regulates levels of dopamine (DA) and norepinephrine (NE) in several cerebral regions, inactivates postsynaptic CA and protects dopaminergic neurons from the free radicals generated by the oxidative metabolism of DA.
References
1.Mamidi S, et al. Immunobiology. 2017 Jan;222(1):45-54.
1.Bastos P,et al. Rev Physiol Biochem Pharmacol. 2017;173:1-39.
Metabolic Enzyme/Protease
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DGAT(4)
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Factor Xa(22)
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