ENTRIES A–Z
Philip Winn in Dictionary of Biological Psychology, 2003
CATECHOL-O-METHYLTRANSFERASE (COMT). (Both MONOAMINE OXIDASE-A and MONOAMINE OXIDASE-B effectively degrade noradrenaline.) Monoamine oxidase destruction of noradrenaline leads to formation of the metabolite 3,4-DIHYDROXYPHENYLGLYCOACETALDEHYDE (DHPGA): ALDEHYDE DEHYDROGENASE further con-verts this to 3,4-DIHYRODXYMANDELIC ACID (DHMA), which COMT then degrades to VAN-ILLYMANDELIC ACID (VMA). DHPGA can also be converted by ALDEHYDE REDUCTASE to 3,4- DIHYDROXYPHENYLGLYCOL (DHPG) which COMT converts to 3-METHOXY-4- HYDROXYPHENYLGLYCOL (MHPG). COMT destruction of noradrenaline itself leads to production of the metabolite NORMETANEPHRINE (NMN) which monoamine oxidase can convert to 3-METHOXY-4-HYDROXYPHENYLGLYCOALDEHYDE (MHPGA). MHPGA can be further converted by aldehyde dehydrogenase to produce a VMA and MHPG. Measurement of the metabolites of noradrenaline (or indeed any other neurochemical) can give important information regarding its synthesis in brain.
Velo-cario-Facial Syndrome
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
A number of studies have proposed candidate genes within the deleted region in relation to specific anomalies or groups of anomalies (29–32). At this time, it seems likely that at least two genes can be linked to some of the VCFS phenotype. Because the 22q11.2 genome is well preserved across species, its homolog has been isolated to mouse chromosome 16. Using animal models, investigators have determined that haploin-sufficiency of the gene TBX1 results in the same conotruncal heart anomalies commonly found inVCFS (31). The gene COMT (catechol-O-methyltransferase) has been linked to psychiatric disorders in relation to the metabolism and degradation of synaptic dopamine levels (30,33). COMT is responsible for the degradation of dopamines and therefore has been hypothesized to have an effect on neural transmission. COMT has been found to have a polymorphism, two alleles that have different activity levels with regard to their ability to degrade dopamines: a low secreting heat labile version, and a high secreting stable version (30). Hemizygosity for the low secreting version has been linked to a higher frequency of psychiatric disorders in individuals with VCFS (30). Both of these genes reside within the commonly deleted region for VCFS and all individuals who are FISH positive for the deletion will be missing single copies of TBX1 and COMT.
The Crucial Role of Craniofacial Growth on Airway, Sleep, and the Temporomandibular Joint
Aruna Bakhru in Nutrition and Integrative Medicine, 2018
Genetic marker studies of genes involved with catecholamine metabolism and adrenergic receptors suggest that certain polymorphisms (e.g., in the catechol O-methyltransferase [COMT] gene) might be associated with changes in pain responsiveness and pain processing in patients with chronic temporomandibular disorders (Diatchenko, Nackley et al. 2006, Diatchenko, Anderson et al. 2006). Differences in pain modulation have been shown between women and men with these disorders, with women showing decreased thresholds to noxious stimuli and more hyperalgesia. In addition, some studies suggest that the affective component of pain in women with temporomandibular disorders may be enhanced during the low-estrogen phase of the menstrual cycle (Bhalang et al. 2005, Diatchenko et al. 2005, Bragdon et al. 2002, de Leeuw et al. 2006).
Evaluation of COMT (rs4680), CNR2 (rs2501432), CNR2 (rs2229579), UCP2 (rs659366), and IL-17 (rs763780) gene variants in synthetic cannabinoid use disorder patients
Published in Journal of Addictive Diseases, 2020
Sacide Pehlivan, Hasan Mervan Aytac, Selin Kurnaz, Mustafa Pehlivan, Pinar Cetinay Aydin
Catechol-O-methyltransferase (COMT) is an enzyme found in the central nervous system that inactivates dopamine, epinephrine, and norepinephrine. A variation in the COMT gene exchanging valine to the methionine amino acid at position 108/158 results in two common enzyme variants: Val and Met. While the Met allele of COMT is associated with low enzymatic activity, the Val allele is associated with increased enzymatic activity.5 COMT (rs4680) variants may affect COMT activity in the brain, altering dopamine neurotransmission known to play a prominent role in reward and addiction.6 Cannabinoid receptors that bind to both exogenous and endogenous cannabinoids are seven-transmembrane domain G-protein-coupled receptors. The cannabinoid receptor-1 (CB1) is encoded by the cannabinoid receptor type 1 (CNR1) gene, while the cannabinoid receptor-2 (CB2) is encoded by the cannabinoid receptor type 2 gene (CNR2), which has been actively investigated for its role in osteoporosis, inflammation, leukemia, several types of cancer, and addiction.7
CNR2 rs2229579 and COMT Val158Met variants, but not CNR2 rs2501432, IL-17 rs763780 and UCP2 rs659366, contribute to susceptibility to substance use disorder in the Turkish population
Published in Psychiatry and Clinical Psychopharmacology, 2019
Selin Kurnaz, Ahmet Bulent Yazici, Ayse Feyda Nursal, Pinar Cetinay Aydin, Ayca Ongel Atar, Nazan Aydin, Zeliha Kincir, Sacide Pehlivan
Catechol-O-methyltransferase (COMT) is an enzyme found all over the mammalian central nervous system which breaks down the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. A common G-to-A transition in exon 4 of the COMT gene, causing a valine (val)-to-methionine (met) substitution at the amino acid position 108 or 158 (depending on the splice variant), results in a four-fold reduction in enzyme activity in met homozygotes, whereas heterozygotes manifest intermediate activity [3]. The endocannabinoid system plays a role in susceptibility to substance abuse. There are two well-defined cannabinoid receptors (CNRs), CNR1/CB1 and CNR2/CB2, that mediate endocannabinoid signalling [4]. CNR2 has been classically defined as the peripheral cannabinoid receptor because CNR2 is expressed principally in some peripheral and immune cells [5]. Uncoupling protein 2 (UCP2) is a member of an anion-carrier protein family found in the mitochondrial inner membrane. In the central nervous system, mammalian UCP2 mRNA and protein expression occurs at highest levels in regions that could be described as high-risk for stress [6]. The Interleukin 17 (IL-17 or IL-17A) is a fundamental pro-inflammatory cytokine that is primarily released from T cells and is now believed to be the defining cytokine of a recently discovered new subset of T-helper cells, Th17 [7]. New studies have reported that cells of the central nervous system also express IL-17.
Comparative examination of levodopa pharmacokinetics during simultaneous administration with lactoferrin in healthy subjects and the relationship between lipids and COMT inhibitory activity in vitro
Published in Nutritional Neuroscience, 2022
Masahiro Nagai, Madoka Kubo, Rina Ando, Masayuki Ikeda, Hiroshi Iwamoto, Yasuhiro Takeda, Masahiro Nomoto
Catechol-O-methyltransferase (COMT) is an enzyme that metabolizes biologically active substances, including catechols and methylated hydroxyl groups using S-adenosylmethionine as a methyl donor. It is widely distributed in living tissues and metabolizes biologically active substances, including the neurotransmitters dopamine and noradrenaline [4]. COMT is expressed as a membrane-bound and soluble isoform, and neurotransmitters are inactivated at neuronal synapses by these enzymes. COMT inhibitors, such as entacapone, have been studied for a long time and are used for the treatment of Parkinson’s disease (PD) [5]. As natural derivatives, epigallocatechin gallate and quercetin are known to exhibit COMT inhibitory effects [6,7]. COMT inhibitors inhibit the metabolism of levodopa in the treatment of PD and are used in combination with carbidopa and benserazide aromatic amino acid decarboxylase inhibitors (DCI) to enhance the brain entry (Figure 1).
Related Knowledge Centers
- Adrenaline
- Catechol
- Enzyme
- Methyl Group
- Catecholamine
- Norepinephrine
- Dopamine
- Neurotransmitter
- Catechol Estrogen
- Gene