Enzyme that catalyzes the movement of a methyl group from S-adenosylmethionone to a catechol or a catecholamine.
A selective serotonin reuptake inhibitor that is used in the treatment of DEPRESSION and a variety of ANXIETY DISORDERS.
Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.
A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.
A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.
A sulfur-containing essential L-amino acid that is important in many body functions.
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
2- or 4-Hydroxyestrogens. Substances that are physiologically active in mammals, especially in the control of gonadotropin secretion. Physiological activity can be ascribed to either an estrogenic action or interaction with the catecholaminergic system.
A group of 1,2-benzenediols that contain the general formula R-C6H5O2.
Occupations of medical personnel who are not physicians, and are qualified by special training and, frequently, by licensure to work in supporting roles in the health care field. These occupations include, but are not limited to, medical technology, physical therapy, physician assistant, etc.
A 30-kDa COMPLEMENT C1Q-related protein, the most abundant gene product secreted by FAT CELLS of the white ADIPOSE TISSUE. Adiponectin modulates several physiological processes, such as metabolism of GLUCOSE and FATTY ACIDS, and immune responses. Decreased plasma adiponectin levels are associated with INSULIN RESISTANCE; TYPE 2 DIABETES MELLITUS; OBESITY; and ATHEROSCLEROSIS.
The infusion of leaves of CAMELLIA SINENSIS (formerly Thea sinensis) as a beverage, the familiar Asian tea, which contains CATECHIN (especially epigallocatechin gallate) and CAFFEINE.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
The physiological period following the MENOPAUSE, the permanent cessation of the menstrual life.
Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.
Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.
The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.
An inhibitor of DOPA DECARBOXYLASE that does not enter the central nervous system. It is often given with LEVODOPA in the treatment of parkinsonism to prevent the conversion of levodopa to dopamine in the periphery, thereby increasing the amount that reaches the central nervous system and reducing the required dose. It has no antiparkinson actions when given alone.
Agents used in the treatment of Parkinson's disease. The most commonly used drugs act on the dopaminergic system in the striatum and basal ganglia or are centrally acting muscarinic antagonists.
An inhibitor of DOPA DECARBOXYLASE, preventing conversion of LEVODOPA to dopamine. It is used in PARKINSON DISEASE to reduce peripheral adverse effects of LEVODOPA. It has no antiparkinson actions by itself.
Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous SPRAINS AND STRAINS; INTERVERTEBRAL DISK DISPLACEMENT; and other conditions.
Degenerative changes in the INTERVERTEBRAL DISC due to aging or structural damage, especially to the vertebral end-plates.
VERTEBRAE in the region of the lower BACK below the THORACIC VERTEBRAE and above the SACRAL VERTEBRAE.
Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.
Acute or chronic pain located in the posterior regions of the THORAX; LUMBOSACRAL REGION; or the adjacent regions.
An INTERVERTEBRAL DISC in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region.
Marked depression appearing in the involution period and characterized by hallucinations, delusions, paranoia, and agitation.
A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION).
An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.
The combined effects of genotypes and environmental factors together on phenotypic characteristics.
An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.
The feeling-tone accompaniment of an idea or mental representation. It is the most direct psychic derivative of instinct and the psychic representative of the various bodily changes by means of which instincts manifest themselves.
Stress wherein emotional factors predominate.
The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.
Genotypic differences observed among individuals in a population.

In vivo effects of new inhibitors of catechol-O-methyl transferase. (1/735)

1. The effects of two new synthetic compounds showing in vitro catechol-O-methyl transferase (COMT) inhibitor properties were studied in vivo and compared with the effects of nitecapone and Ro-41-0960. 2. QO IA (3-(3-hydroxy-4-methoxy-5-nitrobenzylidene)-2,4-pentanedione), QO IIR ([2-(3,4-dihydroxy-2-nitrophenyl)vinyl]phenyl ketone), nitecapone and Ro-41-0960 (30 mg kg(-1), i.p.) were given to reserpinized rats 1 h before the administration of L-DOPA/carbidopa (LD/CD, 50:50 mg kg(-1), i.p.). Locomotor activity was assessed 1 h later. All the COMT inhibitors (COMTI), with the exception of QO IA, markedly potentiated LD/CD reversal of reserpine-induced akinesia. Similar results were obtained when the COMTI were coadministered with LD/CD. The effect of compound QO IIR was dose-dependent (7.5-30 mg kg(-1), i.p.). 3. The COMTI (30 mg kg(-1), i.p.) potentiated LD/CD reversal of both catalepsy and hypothermia of reserpinized mice. 4. QO IIR, nitecapone and Ro-41-0960 (30 mg kg(-1), i.p.) reduced striatal 3-methyl-DOPA (3-OMD) levels and increased dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels. Compound QO IA was devoid of any effect on striatal amine levels. In contrast to the other inhibitors, Ro-41-0961 reduced HVA levels as well. The effect of QO IIR on striatal amine levels was dose-dependent (7.5-60 mg kg(-1), i.p.) 5. These results suggest that the new compound QO IIR is an effective peripherally acting COMT inhibitor in vivo.  (+info)

Dehydrodicaffeic acid dilactone, an inhibitor of catechol-O-methyl transferase. (2/735)

In the screening of catechol-O-methyltransferase inhibitors, three compounds were isolated from the culture filtrate of a mushroom, Inonotus sp. One was 3,4-dihydroxycinnamic acid (caffeic acid) which had been reported as an inhibitor of this enzyme. The others were the dextrorotatory 2,6-bis-(3',4'-dihydroxyphenyl)-3,7-dioxabicyclo-[3,3,0]-octane 4,8-dione (dehydrodicaffeic acid dilactone) andits antipode. These new compounds inhibited both dopamine beta-hydroxylase and dopa decarboxylase and showed hypotensive activity in the SH rat.  (+info)

Characterization and implications of estrogenic down-regulation of human catechol-O-methyltransferase gene transcription. (3/735)

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is a ubiquitous enzyme that is crucial to the metabolism of carcinogenic catechols and catecholamines. Regulation of human COMT gene expression may be important in the pathophysiology of various human disorders including estrogen-induced cancers, Parkinson's disease, depression, and hypertension. The gender difference in human COMT activity and variations in rat COMT activity during the estrous cycle led us to explore whether estrogen can regulate human COMT gene transcription. Our Northern analyses showed that physiological concentrations of 17-beta-estradiol (10(-9)-10(-7) M) could decrease human 1. 3-kilobase COMT mRNA levels in MCF-7 cells in a time- and dose-dependent manner through an estrogen receptor-dependent mechanism. Two DNA fragments immediately 5' to the published human COMT gene proximal and distal promoters were cloned. Sequence analyses revealed several half-palindromic estrogen response elements and CCAAT/enhancer binding protein sites. By cotransfecting COMT promoter-chloramphenicol acetyltransferase reporter genes with human estrogen receptor cDNA and pSV-beta-galactosidase plasmids into COS-7 cells, we showed that 17-beta-estradiol could down-regulate chloramphenicol acetyltransferase activities, and COMT promoter activities dose-dependently. Functional deletion analyses of COMT promoters also showed that this estrogenic effect was mediated by a 280 base pair fragment with two putative half-palindromic estrogen response elements in the proximal promoter and a 323-base pair fragment with two putative CCAAT/enhancer binding protein sites in the distal promoter. Our findings provide the first evidence and molecular mechanism for estrogen to inhibit COMT gene transcription, which may shed new insight into the role of estrogen in the pathophysiology of different human disorders.  (+info)

Interactions of (-)-ilimaquinone with methylation enzymes: implications for vesicular-mediated secretion. (4/735)

BACKGROUND: The marine sponge metabolite (-)-ilimaquinone has antimicrobial, anti-HIV, anti-inflammatory and antimitotic activities, inhibits the cytotoxicity of ricin and diptheria toxin, and selectively fragments the Golgi apparatus. The range of activities demonstrated by this natural product provides a unique opportunity for studying these cellular processes. RESULTS: Affinity chromatography experiments show that (-)-ilimaquinone interacts with enzymes of the activated methyl cycle: S-adenosylmethionine synthetase, S-adenosylhomocysteinase and methyl transferases. Known inhibitors of these enzymes were found to block vesicle-mediated secretion in a manner similar to (-)-ilimaquinone. Moreover, the antisecretory effects of (-)-ilimaquinone and inhibitors of methylation chemistry, but not brefeldin A, could be reversed in the presence of the cellular methylating agent S-adenosylmethionine. Of the enzymes examined in the activated methyl cycle, S-adenosylhomocysteinase was specifically inhibited by (-)-ilimaquinone. Consistent with these observations, (-)-ilimaquinone was shown to obstruct new methylation events in adrenocorticotrophic hormone (ACTH)-secreting pituitary cells. CONCLUSIONS: (-)-ilimaquinone inhibits cellular methylations through its interactions with S-adenosylhomocysteinase. Furthermore, these studies indicate that the inhibition of secretion by ilimaquinone is the result of the natural product's antimethylation activity. It is likely that the ability to fragment the Golgi apparatus, as well as other activities, are also related to ilimaquinone's influence on methylation chemistry.  (+info)

COMT inhibition with tolcapone does not affect carbidopa pharmacokinetics in parkinsonian patients in levodopa/carbidopa (Sinemet). (5/735)

AIMS: Tolcapone is a novel catechol-O-methyltransferase (COMT) inhibitor used as an adjunct to levodopa/carbidopa or levodopa/benserazide therapy to improve treatment of Parkinson's disease. The aim of the current study was to investigate the potential effect of tolcapone on the pharmacokinetics of carbidopa. METHODS: This was an open-label study in 12 parkinsonian patients receiving optimal levodopa/carbidopa therapy and tolcapone 200 mg three times daily for 6 weeks. Blood samples were taken at baseline (i.e. before the first tolcapone intake) and after 1-2 weeks and 6 weeks so that carbidopa pharmacokinetics before and during tolcapone treatment could be assessed. RESULTS: No changes in any pharmacokinetic parameters of carbidopa were observed. The mean AUC(0,tau) and Cmax values at baseline were 0.39 microg ml-1 h and 0. 14 microg ml-1, respectively. During tolcapone treatment these values were on average 0.35 microg ml-1 h (AUC(0,tau), week 1-2), 0. 34 microg ml-1 h (AUC(0,tau), week 6 and 0.13 microg ml-1 (Cmax, weeks 1-2 and 6). tmax remained unchanged (approx. 2 h). CONCLUSIONS: These results indicate that tolcapone does not affect carbidopa elimination and that no interaction of any clinical relevance occurs between tolcapone and carbidopa.  (+info)

Catechol-O-methyltransferase activity in CHO cells expressing norepinephrine transporter. (6/735)

1. We examined the existence of catecholamine metabolizing enzymes (catechol-O-methyltransferase, COMT, and monoamine oxidase, MAO) in CHO cells transfected with norepinephrine (NE) transporter (NET) cDNA. 2. NET activity was studied by incubating cells with [3H]-NE (0. 5 microCi ml-1, 20 min) in a Na+ containing medium. Incubation with [3H]-NE lead to [3H] accumulation at 47797+/-4864 d.p.m. per well. Specific inhibitors of NET abolished this uptake. 3. During post-uptake incubation, [3H] leaked rapidly from cells and the extracellular phase comprised 89% of total radioactivity within 40 min. Both [3H] retention and [3H] 'leakage' were largely unaffected by inhibitors for MAO. In contrast, COMT inhibitors, U-0521 and Ro 41-0960, dose-dependently increased intracellular [3H]-NE retention with a maximal increase of 4.5 fold. The EC50 for Ro 41-0960 was 139-times lower than that of U-0521. U-0521 largely inhibited [3H] 'leakage' and doubled the apparent Vmax for [3H]-NE uptake. 4. Addition of U-0521 during uptake incubation increased intracellular NE content by 8 fold. Normetanephrine, the COMT-dependent metabolite of NE, was formed in large quantities during post-uptake incubation. U-0521 significantly inhibited the formation of NMN with an equal preservation of intracellular NE. 5. CHO cells expressing NET possess COMT activity, which is responsible for the metabolism of NE to form lipophilic metabolite normetanephrine. The apparent 'properties' of the NET function expressed in CHO cells changed, after inhibition of COMT, in such a way closer to that described in the native neuronal preparations.  (+info)

Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility. (7/735)

Estrogen has been proposed to trigger breast cancer development via an initiating mechanism involving its metabolite, catechol estrogen (CE). To examine this hypothesis, we conducted a multigenic case-control study to determine whether polymorphisms of the genes responsible for CE formation via estrogen biosynthesis (CYP17) and hydroxylation (CYP1A1) and CE inactivation (COMT) are associated with an elevated risk for breast cancer in Taiwanese women, and whether the association between genotype and risk may be modified by estrogen exposure. One hundred and fifty breast cancer patients and 150 healthy controls were recruited. PCR-based RFLP assays were used to determine the genotypes of estrogen-metabolizing genes. The breast cancer risk associated with individual susceptibility genotypes varied among the three genes and was highest for COMT, followed by CYP1A1 and CYP17. After simultaneous consideration of all three genes and other well-established risk factors of breast cancer, the COMT genotype remained the most significant determinant for breast cancer development and was associated with a 4-fold increase in risk (95% confidence interval, 1.12-19.08). Furthermore, a trend of increasing risk for developing breast cancer was found in women harboring higher numbers of high-risk genotypes (P = 0.006), including the high activity CYP17 (CYP17 A2/A2), high inducibility CYP1A1 (CYP1A1 MspI vt/vt), and low activity COMT (COMT L/L) genotypes. The association of risk with the number of susceptibility genotypes was stronger in women with prolonged estrogen exposure (indicated by a higher number of estrogen exposure years or a higher number of estrogen exposure years between menarche and first full-term pregnancy), women with higher estrogen levels (implied by early menarche), and women with a higher body mass index (> or = 22.5). On the basis of comprehensive profiles of estrogen metabolism, this study supports the possibility that breast cancer can be initiated by estrogen exposure.  (+info)

Increased mitochondrial superoxide production in rat liver mitochondria, rat hepatocytes, and HepG2 cells following ethinyl estradiol treatment. (8/735)

Ethinyl estradiol (EE) is a strong promoter of hepatocarcinogenesis. Treatment of rats with EE and other hepatic promoters induces a mitosuppressed state characterized by decreased hepatocyte turnover and reduced growth responsiveness. Previously, we identified several nuclear and mitochondrial genome-encoded mitochondrial genes whose transcripts were increased during EE-induced hepatic mitosuppression in rats and in EE-treated HepG2 cells (Chen et al. Carcinogenesis, 17, 2783-2786, 1996 and Carcinogenesis, 19, 101-107, 1998). In both cultured rat hepatocytes and HepG2 cells, EE increased respiratory chain activity (reflected by increased mitochondrial superoxide production detected as increased lucigenin-derived chemiluminescence (LDCL). In this paper, we provide additional characterizations of these effects. Increased LDCL was detected in mitochondria isolated from EE-treated rats, documenting that these estrogen effects on mitochondrial function are not confined to cells in culture. EE and estradiol (E2) increased LDCL in cultured rat hepatocytes and HepG2 cells in a dose- (beginning at 0.25 microM levels) and time-dependent response. Inhibition of P450-mediated estrogen metabolism inhibited, while direct exposure to E2 catechol metabolites enhanced LDCL. Co-treatment with glutathione ester or with the specific antiestrogen, ICI 182708 inhibited LDCL. In contrast, estrogen-induced LDCL was enhanced by glutathione depletion, and by inhibition of catechol-o-methyltransferase. These results support a working hypothesis that in liver cells, increased respiratory chain activity induced by estrogen treatment requires both metabolism to catechols and an estrogen receptor-mediated signal transduction pathway.  (+info)

TY - JOUR. T1 - Contribution of catechol O-methyltransferase to the removal of accumulated interstitial catecholamines evoked by myocardial ischemia. AU - Kuroko, Yosuke. AU - Fujii, Takafumi. AU - Yamazaki, Toji. AU - Akiyama, Tsuyoshi. AU - Ishino, Kozo. AU - Sano, Shunji. AU - Mori, Hidezo. PY - 2005/11/11. Y1 - 2005/11/11. N2 - Catechol O-methyltransferase (COMT) plays an important role for clearance of high catecholamine levels. Although myocardial ischemia evokes similar excessive catecholamine accumulation, it is uncertain whether COMT activity is involved in the removal of accumulated catecholamines evoked by myocardial ischemia. We examined how COMT activity affects myocardial catecholamine levels during myocardial ischemia and reperfusion. We implanted a dialysis probe into the left ventricular myocardial free wall and measured dialysate catecholamines levels in anesthetized rabbits. Dialysate catecholamine levels served as an index of myocardial interstitial catecholamine levels. We ...
TY - JOUR. T1 - L-DOPA biotransformation. T2 - Correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with metabolic pathways in Parkinsonian patients. AU - Dousa, M. K.. AU - Weinshilboum, Richard M. AU - Muenter, M. D.. AU - Offord, K. P.. AU - Decker, P. A.. AU - Tyce, G. M.. PY - 2003/8/1. Y1 - 2003/8/1. N2 - The objectives of this study were to determine (1) the effects of dose and drug absorption on pathways of biotransformation of L-DOPA in Parkinsonian patients treated with Sinemet, and (2) the extent to which genetically-determined variations in the activities of erythrocyte catechol O-methyltransferase and/or platelet phenol sulfotransferase might be reflected in individual differences in L-DOPA metabolism. In the 19 patients studied, there were negative correlations between dosage or absorption and extent of O-methylation and of sulfation of L-DOPA or its metabolites. Levels of activity for erythrocyte COMT were also reflected in individual ...
TY - JOUR. T1 - The catechol-O-methyltransferase polymorphism. T2 - Relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. AU - Bilder, Robert M.. AU - Volavka, Jan. AU - Lachman, Herbert M.. AU - Grace, Anthony A.. PY - 2004/11/1. Y1 - 2004/11/1. N2 - Diverse phenotypic associations with the catechol-O-methyltransferase (COMT) Val158Met polymorphism have been reported. We suggest that some of the complex effects of this polymorphism be understood from the perspective of the tonic-phasic dopamine (DA) hypothesis. We hypothesize that the COMT Met allele (associated with low enzyme activity) results in increased levels of tonic DA and reciprocal reductions in phasic DA in subcortical regions and increased D1 transmission cortically. This pattern of effects is hypothesized to yield increased stability but decreased flexibility of neural network activation states that underlie important aspects of working memory and executive functions; these effects may be beneficial or ...
TY - JOUR. T1 - A single-nucleotide polymorphism in the fetal catechol-o-methyltransferase gene is associated with spontaneous preterm birth in African Americans. AU - Thota, Chandrasekhar. AU - Menon, Ramkumar. AU - Wentz, Melissa J.. AU - Fortunato, Stephen J.. AU - Bartlett, Jackie. AU - Drobek, Cayce O.. AU - Nair, Sangeeta. AU - Al-Hendy, Ayman. PY - 2012/2. Y1 - 2012/2. N2 - Catechol-O-methyltransferase (COMT) activity has been reported to be higher in African Americans (AA) than Caucasians (Cau). COMT converts 2- and 4-hydroxy (OH) estrogens to 2- and 4-methoxyestrogens, respectively, and can increase estrogenic milieu locally in tissues. To assess whether the increased incidence of preterm birth (PTB) among AA women is associated with single-nucleotide polymorphism (SNP) in the COMT gene, we examined variations in maternal and fetal COMT genes and their association with pregnancy outcomes (term vs preterm pregnancies) using 4 functional SNPs: rs4633, rs4680, rs4818, and rs6269 in both AA ...
BACKGROUND: Catechol-O-methyltransferase (COMT) metabolizes dopamine. The COMT Val(158)Met polymorphism influences its activity, and multiple neural correlates of this genotype on dopaminergic phenotypes, especially working memory, have been reported. COMT activity can also be regulated pharmacologically by COMT inhibitors. The inverted-U relationship between cortical dopamine signaling and working memory predicts that the effects of COMT inhibition will differ according to COMT genotype. METHODS: Thirty-four COMT Met(158)Met (Met-COMT) and 33 COMT Val(158)Val (Val-COMT) men were given a single 200-mg dose of the brain-penetrant COMT inhibitor tolcapone or placebo in a randomized, double-blind, between-subjects design. They completed the N-back task of working memory and a gambling task. RESULTS: In the placebo group, Met-COMT subjects outperformed Val-COMT subjects on the 2- back, and they were more risk averse. Tolcapone had opposite effects in the two genotype groups: it worsened N-back performance
Catechol-O-methyltransferase (COMT; EC 2.1.1.6) is one of several enzymes that degrade catecholamines (such as dopamine, epinephrine, and norepinephrine), catecholestrogens, and various drugs and substances having a catechol structure. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene. Two isoforms of COMT are produced: the soluble short form (S-COMT) and the membrane bound long form (MB-COMT). As the regulation of catecholamines is impaired in a number of medical conditions, several pharmaceutical drugs target COMT to alter its activity and therefore the availability of catecholamines. COMT was first discovered by the biochemist Julius Axelrod in 1957. Catechol-O-methyltransferase is involved in the inactivation of the catecholamine neurotransmitters (dopamine, epinephrine, and norepinephrine). The enzyme introduces a methyl group to the catecholamine, which is donated by S-adenosyl methionine (SAM). Any compound having a catechol structure, like catecholestrogens and ...
The prefrontal cortex (PFC) dopamine system, which is critical for modulating PFC function, undergoes remodeling until at least young adulthood in primates. Catechol-o-methyltransferase (COMT) alters extracellular dopamine levels in PFC, and its gene contains a functional polymorphism (Val(158)Met) that has been associated with variation in PFC function. We examined COMT enzyme activity and protein immunoreactivity in the PFC during human postnatal development. Protein was extracted from PFC of normal individuals from 6 age groups: neonates (1-4 months), infants (5-11 months), teens (14-18 years), young adults (20-24 years), adults (31-43 years), and aged individuals (68-86 years; n = 5-8 per group). There was a significant 2-fold increase in COMT enzyme activity from neonate to adulthood, paralleled by increases in COMT protein immunoreactivity. Furthermore, COMT protein immunoreactivity was related to Val(158)Met genotype, as has been previously demonstrated. The significant increase in COMT activity
Catechol-O-methyltransferase (COMT Val158Met) has been implicated in both depression and cardiovascular disease. The purpose of this study was to assess if COMT Val158Met, which influences the COMT enzyme activity, has an effect on the risk of cardiovascular disease (CVD) in individuals with a history of depression and also to determine if the risk differs depending on gender. Data from a longitudinal cohort study of mental health among Swedish adults was used. Depression was assessed twice 3 years apart for each participant, in 1998-2001 and 2001-2003. Saliva DNA was contributed by 4349 (41.7%) of the participants and 3525 was successfully genotyped for COMT Val158Met. Participants were followed up until December 2014 from the National Patient register with regard to cardiovascular outcomes (hypertensive or ischemic heart disease, and stroke). Those with depression and the high COMT enzyme activity genotype (Val/Val) had almost a three-fold increased risk of later CVD (OR 3.6; 95% CI: 2.0-6.6) compared
Metabolites of entacapone, (E)-2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl) propenamide, a potent inhibitor of catechol-O-methyltransferase, were isolated from dog urine. After hydrolysis of glucuronides and sulfates, 5 metabolites were identified in addition to unchanged entacapone by HPLC w …
The effect of catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain structure and function has been previously investigated separately and regionally; this prevents us from obtaining a full picture of the effect of this gene variant. Additionally, gender difference must not be overlooked because estrogen exerts an interfering effect on COMT activity. We examined 323 young healthy Chinese Han subjects and analyzed the gray matter volume (GMV) differences between Val/Val individuals and Met carriers in a voxel-wise manner throughout the whole brain. We were interested in genotype effects and genotype x gender interactions. We then extracted these brain regions with GMV differences as seeds to compute resting-state functional connectivity (rsFC) with the rest of the brain; we also tested the genotypic differences and gender interactions in the rsFCs. Val/Val individuals showed decreased GMV in the posterior cingulate cortex (PCC) compared with Met carriers; decreased GMV in the medial ...
Catechol-O-methyl transferase Catechol-O-methyltransferase Identifiers Symbol(s) COMT; External IDs OMIM: 116790 MGI: 88470 Homologene: 30982
We investigated whether the val(158)met functional polymorphism of catechol-o-methyltransferase influenced age-related changes in grey matter density and volume, both in healthy individuals (n=80, ages 18-79) and those with Parkinsons disease (n=50). Global grey matter volumes and voxelwise estimates of grey matter volume and density were determined from structural magnetic resonance images at 3T. Male and female ValVal homozygotes (low prefrontal cortical dopamine) had more grey matter in early adulthood, but this difference disappeared with increasing age. The insula and ventral prefrontal cortex had higher grey matter volume in younger, but not older, ValVal homozygotes. Conversely, the dominant premotor cortex revealed genotypic differences in grey matter density in later life. There were no global or local interactions between Parkinsons disease and COMT val(158)met genotype on morphometry. Since the val(158)met polymorphism is associated with differences in cortical dopamine metabolism, our data
Dose-response curves of increase in pupil size and decrease in intraocular pressure with topical epinephrine have been determined in the sympathetically denervated rabbit eye. Topical pretreatment with the catechol-O-methyl transferase inhibitor U-0521 potentiated the effects of epinephrine on both the pupil and pressure. These observations suggest a possible role for catechol-O-methyl transferase in the aqueous humor dynamics of the supersensitive eye. The possible use of the denervated rabbit eye as an experimental model for the glaucomatous eye in evaluating the ocular effects of adrenergic agents is discussed.. ...
Catechol-O-methyltransferase (COMT) modulates dopamine in the prefrontal cortex (PFC) and influences PFC dopamine-dependent cognitive task performance. A human COMT polymorphism (Val(158)Met) alters enzyme activity and is associated with both the activation and functional connectivity of the PFC during task performance, particularly working memory. Here, we used functional magnetic resonance imaging and a data-driven, independent components analysis (ICA) approach to compare resting state functional connectivity within the executive control network (ECN) between young, male COMT Val(158) (n=27) and Met(158) (n=28) homozygotes. COMT genotype effects on grey matter were assessed using voxel-based morphometry. COMT genotype significantly modulated functional connectivity within the ECN, which included the head of the caudate, and anterior cingulate and frontal cortical regions. Val(158) homozygotes showed greater functional connectivity between a cluster within the left ventrolateral PFC and the rest of
Catechol O-methyltransferase (COMT) is a ubiquitous bisubstrate magnesium-dependent enzyme found in plants, animals and microorganisms. COMT catalyses the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to one of the hydroxyl oxygen atoms (preferentially the 3-hydroxyl) in a catechol substrate. Physiological substrates of COMT are catecholamine neurotransmitters such as dopamine, noradrenaline, adrenaline and their metabolites. COMT also methylates catecholic steroids such as 2-hydroxyestradiol as well as a range of other catecholic compounds including neuroactive drugs such as L-dopa, α-methyldopa and isoproterenol. COMT inhibition is a means of treating Parkinsons disease, schizophrenia and depression. There are two isoforms of human COMT: soluble cytoplasmic COMT (S-COMT), which is mainly intracellular, and a membrane-bound form (MB-COMT), which has a single-span helix contained within a 50 amino acid extension at the N-terminus.. COMT is an enzyme that plays a major role in ...
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
Demethylzeylasteral is among the extracts of Hook F, which has important assignments in multiple biological procedures such as irritation inhibition, aswell as immunosuppression. thus inhibits its ubiquitin-dependent degradation. Jointly, demethylzeylasteral is normally a appealing anti-tumor substance in melanoma cells. Demethylzeylasteral can be a potential inhibitor of MCL1. Melanoma can be known as malignant melanoma from melanocytes.1 Surgical resection may be the main way for sufferers NSC 105823 struggling early-stage melanoma.1, 2 Unfortunately, melanoma lesions always stay undetectable,3 which leads to the hold off for melanoma therapy.4, 5 Moreover, melanoma may break out NSC 105823 in later levels,6 when melanoma cells disseminate to varied organs, such as for example human brain, lung or liver organ.2 Consequently, surgical procedure is much less favorable for sufferers. Chemotherapeutic therapy has an important function in cases like this. Theoretically, chemotherapeutic agents ...
Objective The principal goal of the study was to check the disease-modifying aftereffect of blocking a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 using a neutralizing monoclonal antibody (mAb) starting four weeks after destabilization from the medial meniscus (DMM) in the mouse. 4-16 after medical procedures slowed cartilage degeneration and osteophyte growth but did not impact subchondral bone sclerosis. Moreover, ADAMTS-5 blockade resulted in temporary reversal of mechanical allodynia, which correlated with decreased MCP-1 production by cultured DRG cells. Conclusions This study suggests restorative effectiveness of an ADAMTS-5 mAb in the DMM model, when therapy starts early in disease. mice demonstrate long-term safety from cartilage degeneration in experimental OA induced by destabilization of the medial meniscus (DMM) [6] and in antigen-induced arthritis (AIA) [7]. Mechanical allodynia, defined as pain in response to a normally innocuous stimulus, is definitely ...
OBJECTIVE: A valine/methionine polymorphism in the catechol O-methyltransferase (COMT) gene has been proposed to influence susceptibility to schizophrenia, as has a COMT haplotype in Ashkenazi Jewish and Irish subjects. The authors examined these hypotheses. METHOD: They reviewed data from more than 2,800 individuals, including almost 1,200 with schizophrenia, from case-control and family-based European association samples. RESULTS: The authors found no support for the hypothesis that a valine/methionine polymorphism in the COMT gene influences susceptibility to schizophrenia or the hypothesis that a COMT haplotype influences susceptibility to schizophrenia in Ashkenazi Jewish and Irish subjects. CONCLUSIONS: The data suggest that the valine allele of COMT does not increase susceptibility to schizophrenia in Europeans and that the Ashkenazi or Irish haplotype does not increase susceptibility. Ethnic variation in the linkage disequilibrium structure at COMT means that the haplotype data may not ...
Both childhood trauma and a functional COMT genetic polymorphism have been associated with PTSD and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n=38, Met carriers, n=35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD
In the previous post, we investigated the SLC6A4 gene, which is located on the 17th human chromosome, and has a possible (but, at the current time a statistically questionable) preference towards being expressed in ADHD males than in ADHD females.. The second gene on the list, the COMT gene, is also believed to have a male-favoring genetic effect with regards to ADHD individuals. The COMT gene is located on the 22nd human chromosome. COMT is actually an abbreviation for catechol methyltransferase, which is an important enzyme involved in a number of neurological functions which have numerous ADHD-like implications. This important enzyme is coded for by the COMT gene (many genes share a name with the proteins which they encode). Unlike the SLC6A4 gene, this COMT gene has more grounds for statistical significance, both in gender-dependent and overall studies of genes believed to be associated with ADHD.. We have discussed the COMT gene and its role in ADHD in previous posts. We have also ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Decaffeinated GTE was not associated with reductions in body weight, BMI, or WC and did not alter energy intake or mean hormone concentrations in healthy postmenopausal women over 12 mo. GTE decreased fasting insulin concentrations in those with elevated baseline fasting concentrations. The high-act …
BACKGROUND: Neuregulin1 (NRG1)-ErbB signaling has been implicated in the pathogenesis of cancer and schizophrenia. We have previously reported that NRG1-stimulated migration of B lymphoblasts is PI3K-AKT1dependent and impaired in patients with schizophrenia and significantly linked to the catechol-o-methyltransferase (COMT) Val108/158Met functional polymorphism. METHODOLOGY/PRINCIPAL FINDINGS: We have now examined AKT1 activation in NRG1-stimulated B lymphoblasts and other cell models and explored a functional relationship between COMT and AKT1. NRG1-induced AKT1 phosphorylation was significantly diminished in Val carriers compared to Met carriers in both normal subjects and in patients. Further, there was a significant epistatic interaction between a putatively functional coding SNP in AKT1 (rs1130233) and COMT Val108/158Met genotype on AKT1 phosphorylation. NRG1 induced translocation of AKT1 to the plasma membrane also was impaired in Val carriers, while PIP(3) levels were not decreased. Interestingly
Catechol-O-methyltransferase (COMT) is involved in phase II (conjugative) metabolism of catecholamines and catechol drugs, such as dopamine, as well as the catechol-estrogens. COMT transfers a donor methyl-group from S-adenosylmethionine to acceptor hydroxy groups on catechol structures (aromatic ring structures with vicinal hydroxy-groups).(1) Bioactive catecholamine metabolites are metabolized by COMT in conjunction with monoamine oxidase (MAO):. -Norepinephrine is methylated by COMT forming normetanephrine.. -Epinephrine is methylated by COMT forming metanephrine.. -Dopamine is converted to homovanillic acid through the combined action of MAO and COMT.. Parkinsonism patients receiving levodopa (L-DOPA) therapy are frequently also prescribed a COMT inhibitor to minimize metabolism of L-DOPA by COMT, thereby prolonging L-DOPA action.. COMT is also involved in the inactivation of estrogens. Estradiol can be hydroxylated forming the catechol estrogens 2-hydroxyestradiol and 4-hydroxyestradiol.(2) ...
TY - JOUR. T1 - MB-COMT promoter DNA methylation is associated with working-memory processing in schizophrenia patients and healthy controls. AU - Walton, Esther. AU - Liu, Jingyu. AU - Hass, Johanna. AU - White, Tonya. AU - Scholz, Markus. AU - Roessner, Veit. AU - Gollub, Randy. AU - Calhoun, Vince D. AU - Ehrlich, Stefan. PY - 2014/8. Y1 - 2014/8. N2 - Many genetic studies report mixed results both for the associations between COMT polymorphisms and schizophrenia and for the effects of COMT variants on common intermediate phenotypes of the disorder. Reasons for this may include small genetic effect sizes and the modulation of environmental influences. To improve our understanding of the role of COMT in the disease etiology, we investigated the effect of DNA methylation in the MB-COMT promoter on neural activity in the dorsolateral prefrontal cortex during working memory processing as measured by fMRI - an intermediate phenotype for schizophrenia. Imaging and epigenetic data were measured in ...
Background. Treatment outcome of low back pain (LBP) is associated with inter-individual variations in pain relief and functional disability. Genetic variants of catechol-O-methyltransferase (COMT) gene have previously been shown to be associated with pain sensitivity and pain medication. This study examines the association between COMT polymorphisms and 7-11 year change in Oswestry Disability Index (ODI) and Visual Analog Score (VAS) for LBP as clinical outcome variables in patients treated with surgical instrumented lumbar fusion or cognitive intervention and exercise.. Methods. 93 unrelated patients with chronic LBP for duration of >1 year and lumbar disc degeneration (LDD) were treated with lumbar fusion (N = 60) or cognitive therapy and exercises (N = 33). Standardised questionnaires assessing the ODI, VAS LBP, psychological factors and use of analgesics, were answered by patients both at baseline and at 7-11 years follow-up. Four SNPs in the COMT gene were successfully genotyped. Single ...
Catechol-O-methyltransferase (COMT) plays an essential role in degradation of extracellular dopamine in prefrontal regions of the brain. Although a polymorphism in this gene, COMT Val(158)Met, affects human behavior in response to stress little is known about its effect on dopaminergic activity associated with the human stress response, which may be of interest for stress-related psychiatric disorders such as psychosis. We aimed to investigate the effect of variations in COMT genotype on in vivo measures of stress-induced prefrontal cortex (PFC) dopaminergic processing and subjective stress responses. A combined sample of healthy controls and healthy first-degree relatives of psychosis patients (n = 26) were subjected to an [(18)F]fallypride Positron Emission Tomography scan. Psychosocial stress during the scan was induced using the Montreal Imaging Stress Task and subjective stress was assessed every 12 minutes. Parametric t-maps, generated using the linear extension of the simplified reference ...
TY - JOUR. T1 - Association between the catechol-O-methyltransferase (rs4680. T2 - Val158Met) polymorphism and serum alanine aminotransferase activity. AU - Hiyoshi, Mineyoshi. AU - Uemura, Hirokazu. AU - Arisawa, Kokichi. AU - Nakamoto, Mariko. AU - Hishida, Asahi. AU - Okada, Rieko. AU - Matsuo, Keitaro. AU - Kita, Yoshikuni. AU - Niimura, Hideshi. AU - Kuriyama, Nagato. AU - Nanri, Hinako. AU - Ohnaka, Keizo. AU - Suzuki, Sadao. AU - Mikami, Haruo. AU - Kubo, Michiaki. AU - Tanaka, Hideo. AU - Hamajima, Nobuyuki. N1 - Funding Information: This study was supported in part by Grants-in-Aid for Scientific Research on Priority Areas of Cancer (No. 17015018 ) and on Innovative Areas (No. 221S0001 ) from the Japanese Ministry of Education, Culture, Sports, Science and Technology . PY - 2012/4/1. Y1 - 2012/4/1. N2 - In our previous proteomic study in rat liver damaged by carbon tetrachloride, soluble catechol- O-methyltransferase (COMT) increased as a phosphorylated form and decreased as a ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
5 Dopamine Agonists Dopamine agonists directly stimulate the dopamine receptors, with bromocriptine (Parlodel®) and pergolide (Permax®) having been available in Canada for the treatment of PD for many years. More recently, two newer dopamine agonists - ropinirole (Requip®) and pramipexole (Mirapex®) - have become available. These differ from the older compounds in that they are not ergot derivatives, and are therefore devoid of ergot-related side effects such as retroperitoneal or pleural fibrosis. 3 Catechol-O-Methyl Transferase (COMT) Inhibitors Levodopa is metabolized peripherally not only by decarboxylase (as described above) but also by COMT. The latter is a ubiquitous enzyme, and is sufficiently active that when levodopa is administered with a peripheral decarboxylase inhibitor, only about 10% of a given dose will reach the brain intact [15]. Entacapone (Comtan®) inhibits the peripheral metabolism of levodopa by COMT, thereby increasing its availability to the brain, and increasing ...
Introduction: Sex steroids are important for growth and maintenance of the skeleton. Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60-75% difference in enzyme activity between the val (high activity=H) and met (low activity=L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. Methods: Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2822 individuals. Results: Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of ,= 1 fracture was 37.2% in COMTLL, 35.7% in COMTHL and 30.4% in COMTHH (p,0.05). Early fractures (,= 50 years of age) were less common in COMTHH than in the combined COMTLL+HL genotype, ...
Teva-Entacapone: Entacapone belongs to a group of medications called catechol-O-methyl transferase (COMT) inhibitors. It is used along with levodopa-carbidopa or levodopa-benserazide to treat Parkinsons disease.
Received within 4 weeks of Visit 1 or planning to take during participation in the clinical study: any doses of a controlled-release (CR) LD apart from a single daily bedtime dose or any doses of Rytary, additional CD (eg, Lodosyn) or benserazide (eg, Serazide), or catechol-O-methyl transferase inhibitors (entacapone or tolcapone) or medications containing these inhibitors (Stalevo). Received within 4 weeks of Visit 1 or planning to take during participation in the clinical study: nonselective monoamine oxidase (MAO) inhibitors, apomorphine, or dopaminergic blocking agents including antiemetics ...
1292] Mattay, V. S., Goldberg T. E., Fera F., Hariri A. R., Tessitore A., Egan M. F., et al. (2003). Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proceedings of the National Academy of Sciences of the United States of America. 100(10), 6186 - 6191. ...
There is evidence that altering stress mindset-the belief that stress is enhancing vs. debilitating-can change cognitive, affective and physiological responses to stress. However individual differences in responsiveness to stress mindset manipulations have not been explored. Given the previously established role of catecholamines in both placebo effects and stress, we hypothesized that genetic variation in catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, would moderate responses to an intervention intended to alter participants mindsets about stress. Participants (N = 107) were exposed to a stress mindset manipulation (videos highlighting either the enhancing or debilitating effects of stress) prior to engaging in a Trier Social Stress task and subsequent cognitive tasks. The associations of the COMT rs4680 polymorphism with the effect of stress mindset video manipulations on cognitive and affective responses were examined. Genetic variation at rs4680 modified the effects
Quercetin and fisetin, known as catechol-containing flavonoids, could positively affect the absorption of catechins due to their strong affinity for catechol-O-methyl transferase (COMT), which can methylate and cause the excretion of catechins. The current study examined the effect of quercetin and fisetin o
A partially purified preparation of norepinephrine storage particles from the rat heart was studied in vitro. The particles were found to have dopamine β-oxidase activity, indicating that norepinephrine may be formed from dopamine in the storage granules as well as taken up from the cytoplasm of the cell. ATP was found in the particles in the same molar ratio to norepinephrine as has been previously described in adrenal chromaffin granules, and could serve to form a storage complex with the amine. There were only trace amounts of catechol-O-methyl transferase and monoamine oxidase in the preparation. The particles were most stable in solutions at 4°C containing sucrose, magnesium or calcium, but retained about half their catecholamine content in sucrose at 23°C for 1 hour. Norepinephrine was released from the particles into free solution in media of low tonicity or pH, in the presence of the detergent sodium deoxycholate, and by high concentrations of reserpine, tyramine and cocaine. ...
Using an isolated canine heart preparation, the myocardial norepinephrine pool was labeled by injecting tritiated norepinephrine into the blood perfusing the heart. The extraction of the norepinephrine during a single circulation through the coronary bed was shown to be large (74%). As the isotopic material, which was extracted, was released spontaneously from the norepinephrine pool 75% to 88% of it was metabolized before appearing in the coronary venous blood. The chief metabolite has been demonstrated to be normetanephrine which accounts for 39.0% to 61.7% of the spontaneously released norepinephrine. Because of this it is concluded that catechol-O-methyl transferase is the enzyme primarily responsible for the metabolic inactivation of norepinephrine in the canine heart. When release was increased by the injection of tyramine, more of the released norepinephrine appeared unmetabolized in coronary venous blood, suggesting that the enzymatic process by which norepinephrine is inactivated may be ...
Inclusion Criteria:. Idiopathic Parkinsons disease , 7 years duration. Modified Hoehn and Yahr Scale Stages I through III. Age greater than or equal to 30 years old. Patients or their partners must use adequate contraceptive methods. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures and do not plan on traveling extensively during the study. Exclusion Criteria:. Atypical Parkinsons disease syndromes due to drugs, metabolic disorders, encephalitis, or degenerative diseases.. Levodopa received for 1-year accumulated interval in the last two years.. Dopamine agonist medications or catechol-o-methyl transferase inhibitors in the 30 days prior to baseline.. Unstable dose regimes of hypnotics, anxiolytics or antidepressants. Dementia. History of stereotaxic brain surgery, psychosis or active epilepsy within past year.. Participation in clinical trial within the previous 30 days.. Malignant melanoma or history of ...
Nedić, Gordana and Matea Nikolac, Matea and Borovečki, Fran and Hajnšek, Sanja and Muck-Šeler, Dorotea and Pivac, Nela (2010) Association study of a functional catechol-o-methyltransferase polymorphism and smoking in healthy Caucasian subjects. Neuroscience Letters, [Epub . ISSN 0304-3940 ...
The stress of foot shock in rats induces large decreases in the level of brain norepinephrine but does not greatly alter the concentration of serotonin or dopamine in brain. These decrements in norepinephrine are not limited to any region and occur uniformly throughout the brain. However, absolute levels of these amines are not a true indicator of their dynamic state. By various techniques it could be demonstrated that the stress of foot shock accelerates the metabolism of dopamine and serotonin to the same degree as norepinephrine; the only difference being that dopamine and serotonin are rapidly resynthesized, whereas norepinephrine in the brain cannot be regenerated at the same rate. Furthermore, the increased catabolism of brain norepinephrine with stress is blocked by monoamine oxidase inhibitors, whereas catechol-O-methyltransferase inhibitors do not impede accelerated degradation.. ...
Parkinsons disease is a progressive degenerative disorder of the central nervous system. The hallmark physical signs are tremor, rigidity and bradykinesia. Idiopathic Parkinsons disease is caused by the progressive loss of dopaminergic neurons in the substantia nigra and nigrostriatal pathway of the midbrain. Secondary parkinsonism may be caused by certain drugs (e.g., metoclopramide and haloperidol) or by cerebrovascular disease (e.g., multiple lacunar strokes). The disease can usually be diagnosed based on the history and physical findings. Dopamine replacement is still considered the most efficacious treatment for Parkinsons disease, but dopamine agonists, formerly prescribed only as adjunctive therapy, are emerging as useful initial therapy. Other pharmacologic treatments include drugs that inhibit dopamine-metabolizing enzymes (monoamine oxidase-B and catechol O-methyltransferase). Injections of botulinum toxin can be helpful in patients with associated dystonia or blepharospasm. Surgery may be
PRF readers can get free access to a selected Journal of Pain paper each month, thanks to the American Pain Society. Get the free full text of the selection from the December 2017 issue here.. ...
TY - JOUR. T1 - COMT Val158Met genotype is associated with reward learning: A replication study and meta-analysis. AU - Corral-Frías, N. S.. AU - Pizzagalli, D. A.. AU - Carré, J. M.. AU - Michalski, L. J.. AU - Nikolova, Y. S.. AU - Perlis, R. H.. AU - Fagerness, J.. AU - Lee, M. R.. AU - Conley, E. Drabant. AU - Lancaster, T. M.. AU - Haddad, S.. AU - Wolf, A.. AU - Smoller, J. W.. AU - Hariri, A. R.. AU - Bogdan, R.. PY - 2016/6/1. Y1 - 2016/6/1. KW - Anhedonia. KW - COMT. KW - Dopamine. KW - Meta-analysis. KW - Response bias. KW - Reward. KW - Anhedonia. KW - COMT. KW - Dopamine. KW - Meta-analysis. KW - Response bias. KW - Reward. UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84971476742&origin=inward. UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84971476742&origin=inward. U2 - 10.1111/gbb.12296. DO - 10.1111/gbb.12296. M3 - Article. VL - 15. SP - 503. EP - 513. JO - Genes, Brain and Behavior. JF - Genes, Brain and Behavior. SN - ...
Purchase Basic Aspects of Catechol-O-Methyltransferase and the Clinical Applications of its Inhibitors, Volume 95 - 1st Edition. Print Book & E-Book. ISBN 9780123813268, 9780123813275
TY - JOUR. T1 - Regulation of catechol-O-methyltransferase expression in human myometrial cells. AU - Wentz, Melissa J.. AU - Jamaluddin, Mohammad. AU - Garfield, Robert E.. AU - Al-Hendy, Ayman. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2006/12. Y1 - 2006/12. N2 - OBJECTIVE: The catechol-O-methyltransferase enzyme catalyzes the methylation of the catechol estrogens, 2- or 4-hydroxyestrogen, to 2- or 4-methoxyestrogen. Both the hydroxy estrogens and methoxy estrogens were shown to modulate the effects of estrogen. Because catechol-O-methyltransferase activity controls levels of these metabolites, it may help regulate the cellular estrogenic milieu. In this study, we examined the regulation of catechol-O-methyltransferase expression in human myometrial cells. METHODS: Catechol-O-methyltransferase expression was assessed by reverse transcription-polymerase chain reaction, Western blot, and luciferase assays in human myometrial cells after treatment with estrogen or ...
Background Following voxel-based morphometry (VBM), brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been shown to affect human brain morphology in Caucasians. However, little is known about the specific role of the Met/Met genotype on brain structure. Moreover, the relationship between BDNF Val66Met polymorphism and Chinese brain morphology has not been studied. Methodology/Principal Findings The present study investigated brain structural differences among three genotypes of BDNF (rs6265) for the first time in healthy young Chinese adults via cortical thickness analysis and VBM. Brain differences in Met carriers using another grouping method (combining Val/Met and Met/Met genotypes into a group of Met carriers as in most previous studies) were also investigated using VBM. Dual-approach analysis revealed less gray matter (GM) in the frontal, temporal, cingulate and insular cortices in the Met/Met group compared with the Val/Val group (corrected, P|0.05). Areas with less GM
The present study confirms and extends previous findings28 29 that tolcapone enhances the efficacy of levodopa. Whereas initial studies were focused on single dose6 or short term (one to six weeks) multiple dose22 26 coadministration of tolcapone with levodopa/decarboxylase inhibitor, the present study showed that multiple dose (tid) treatment with tolcapone results in reduced severity of wearing off type motor fluctuations in levodopa treated patients for three months and that this response is maintained over time.. Treatment with tolcapone significantly decreased mean off time (by ,20%) and increased mean on time (by ,25%), compared with placebo. Analysis of primary end point on/off data disclosed that both tolcapone dosages were equally effective in increasing on time, but the 100 mg tid dosage was more effective in decreasing off time. However, the mean reduction in levodopa dosage by month 3 was greater with 200 mg tolcapone tid than with 100 mg tid This reduction was maintained ...
Recent evidence suggests that prepulse inhibition (PPI) levels relate to executive function possibly by a prefrontal cortex (PFC) dopamine (DA) link. We explored the effects of enhanced PFC DA signaling by the nonstimulant catechol-O-methyltransferase (COMT) inhibitor tolcapone, on PPI and working memory of subjects homozygous for the Val (low PFC DA) and the Met (high PFC DA) alleles of the COMT Val158Met polymorphism. Twelve Val/Val and eleven Met/Met healthy male subjects entered the study. Tolcapone 200 mg was administered in two weekly sessions, according to a balanced, crossover, double-blind, placebo-controlled design. PPI was assessed with 5 dB and 15 dB above background prepulses, at 30-, 60-, and 120 ms prepulse-pulse intervals. Subjects also underwent the n-back and the letter-number sequencing (LNS) tasks. PPI was lower in the Val/Val compared to the Met/Met group in the placebo condition. Tolcapone increased PPI significantly in the Val/Val group and tended to have the opposite effect in
Identifying mechanisms through which individual differences in reward learning emerge offers an opportunity to understand both a fundamental form of adaptive responding as well as etiological pathways through which aberrant reward learning may contribute to maladaptive behaviors and psychopathology. One candidate mechanism through which individual differences in reward learning may emerge is variability in dopaminergic reinforcement signaling. A common functional polymorphism within the catechol-O-methyl transferase gene (COMT; rs4680, Val158Met) has been linked to reward learning, where homozygosity for the Met allele (linked to heightened prefrontal dopamine function and decreased dopamine synthesis in the midbrain) has been associated with relatively increased reward learning. Here, we used a probabilistic reward learning task to asses response bias, a behavioral form of reward learning, across three separate samples that were combined for analyses (age: 21.80 ± 3.95; n = 392; 268 female; ...
Catechol-O-methyltransferase (COMT) modulates dopamine levels in the prefrontal cortex. The human gene contains a polymorphism (Val158Met) that alters enzyme activity and influences PFC function. It has also been linked with cognition and anxiety, but the findings are mixed. We therefore developed a novel mouse model of altered COMT activity. The human Met allele was introduced into the native mouse COMT gene to produce COMT-Met mice, which were compared with their wild-type littermates. The model proved highly specific: COMT-Met mice had reductions in COMT abundance and activity, compared with wild-type mice, explicitly in the absence of off-target changes in the expression of other genes. Despite robust alterations in dopamine metabolism, we found only subtle changes on certain cognitive tasks under baseline conditions (eg, increased spatial novelty preference in COMT-Met mice vs wild-type mice). However, genotype differences emerged after administration of the COMT inhibitor tolcapone: performance of
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
Jie Tang1 ,Yanjun Li1 ,Jiayuan Xu1 ,Wen Qin1 ,Qian Su2 ,Qiang Xu1 ,Bing Liu3 ,Tianzi Jiang3 ,Chunshui Yu1 1 Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, Peoples Republic of China. 2 School of Medical Imaging and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University, Tianjin, Peoples Republic of China. 3 Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, Peoples Republic of China. Abstract. Catechol-O-methyltransferase (COMT) affects brain connectivity via modulating the dopamine system, with an expected greater effect of haplotypes than single-nucleotide polymorphism (SNP). The action pathway from COMT to dopamine to connectivity is theoretically dependent on the gene expression of dopamine receptors. Here, we aimed to investigate the impact of COMT haplotypes on brain functional connectivity density (FCD) in ...
Normetanephrine is a metabolite of norepinephrine created by action of catechol-O-methyl transferase on norepinephrine. It is excreted in the urine and found in certain tissues. It is a marker for catecholamine-secreting tumors such as pheochromocytoma. ...
Abstract: The COMT gene is thought to contribute to the cognitive/psychiatric phenotypes in 22q11.2 deletion syndrome. We measured these manifestations against the Val/Met alleles of the COMT gene, in 40 nonpsychotic 22q11DS children. The Val allele was associated with poor IQ, processing speed, executive function and a higher frequency of anxiety disorders, underscoring the importance of the COMT gene in the childhood psychopathology in 22q11DS.. COMT and anxiety and cognition in children with chromosome 22q11.2 deletion syndrome ...
Markett, S., Montag, C., Heeren, B., Saryiska, R., Lachmann, B., Weber, B., & Reuter, M. (2016). Voxelwise eigenvector centrality mapping of the human functional connectome reveals an influence of the catechol-O-methyltransferase val158met polymorphism on the default mode and somatomotor network. Brain Structure and Function, 221(5), 2755-2765 ...
Milled wood lignins isolated from genetically modified poplar trees were studied by quantitative 31P NMR spectroscopy, in combination with thioacidolysis and mild alkaline hydrolysis. The genetictransformation of the trees included down regulation of CAD and COMT enzyme activities.These analyses confirmed that moderate CAD down-regulation does not substantially alter ligninstructure. In contrast, severe CAD deficiency alters the lignin structure more profoundly by decreasingthe syringyl/guaiacyl ratio and increasing the degree of condensation of the lignin. Themost severe alterations were observed in the lignins from the COMT-transformed lines ...
BACKGROUND: Recent studies implicate individual differences in regulatory focus as contributing to self-regulatory dysfunction, particularly not responding to positive outcomes. How such individual differences emerge, however, is unclear. We conducted a proof-of-concept study to examine the moderating effects of genetically driven variation in dopamine signaling, a key modulator of neural reward circuits, on the association between regulatory focus and reward cue responsiveness. METHOD: Healthy Caucasians (N=59) completed a measure of chronic regulatory focus and a probabilistic reward task. A common functional genetic polymorphism impacting prefrontal dopamine signaling (COMT rs4680) was evaluated. RESULTS: Response bias, the participants propensity to modulate behavior as a function of reward, was predicted by an interaction of regulatory focus and COMT genotype. Specifically, self-perceived success at achieving promotion goals predicted total response bias, but only for individuals with the ...
The subcutaneous and systemic injection of serotonin reduces cutaneous and visceral pain thresholds and increases responses to noxious stimuli. resonance tests. Based on earlier literature, our determined versions and in vitro outcomes claim that serotonin can be an inhibitor of COMT. Nevertheless, whether this inhibition offers biological significance cant be ascertained from these data only. Our structural model shows that serotonin inhibits COMT activity by positively contending with SAM in the energetic site. This system is definitely further backed by our kinetics research. We performed behavioral tests to see whether our model and in vitro data are predictive of in vivo results on discomfort behaviors. Mice pretreated with SAM shown diminishes serotonin-induced mechanised hypersensitivity (Number ?(Figure3A).3A). We hypothesize that the excess SAM generates this attenuation by reducing the likelihood of serotonin occupying the energetic site of COMT. The fairly modest anti-allodynic ...
She suggested, but did not say, that chronic fatigue syndrome could be triggered as early as pregnancy and then not show up for 20 or 40 or 50 years until another window of vulnerability opens up - perhaps during a stressful period, another infection, toxic overexposure. (She noted that the stress response is similar in all these cases). Indeed, that model of disease, she said, could apply to outbreaks of autism and ADHD in early life, multiple sclerosis, schizophrenia and ME/CFS in middle life and Parkinsons and Alzheimers disease in later life.. Cannabis triggered schizophrenia during adolescence is an example of the three factors combining in a perfect storm to cause a devastating disease. It turns out that bringing together one form of a COMT gene (the COMT gene, oddly enough is implicated in ME/CFS), the tumultuous physiological time of adolescence, and an environmental factor (cannabis) you get an increased risk of (gulp) schizophrenia. Basically smoking pot when youre an adolescent ...
epigallocatechin (EGC) are the major polyphenolic constituents in green tea. Inthis study, we characterized the enzymology of cytosolic catechol-O-methyltransferase(COMT)-catalyzed methylation of EGCG and EGC in humans, mice,and rats. At 1 µM, EGCG was readily methylated by liver cytosolicCOMT to 4-O-methyl-EGCG and then to 4,4-di-O-methyl-EGCG; EGCwas methylated to 4-O-methyl-EGC. The Km and Vmax values forEGC methylation were higher than EGCG; for example, with humanliver cytosol, the Km were 4.0 versus 0.16 µM and Vmax were 1.28 versus 0.16 nmol/mg/min. Rat liver cytosol had higher COMT activitythan that of humans or mice. The small intestine had lower specificactivity than the liver in the methylation of EGCG and EGC. Glucuronidationon the B-ring or the D-ring of EGCG greatly inhibited the methylationon the same ring, but glucuronidation on the A-ring of EGCG orEGC did not affect their methylation. Using EGC and 3,4-dihydroxy-L-phenylalanineas substrates, EGCG, 4-O-methyl-EGCG, and ...
Insulin-Like-Growth Factor 1 Moderates the Influence of the BDNF P.Val66Met Variant on Depression Severity in Adolescent Depression. PubMed, SCI, Scopus, ESCI, PMC indexed
Adeline Galvanin, Lilia Ayadi, Mark Helm, Yuri Motorin, Virginie Marchand. Mapping and Quantification of tRNA 2′-O-Methylation by RiboMethSeq. Methods Mol Biol, pp.273-295, 2019, ⟨10.1007/978-1-4939-8808-2_21⟩. ⟨hal-01957102⟩ ...
MetabolismBiosynthesis of cofactors, prosthetic groups, and carriersMenaquinone and ubiquinone3-demethylubiquinone-9 3-O-methyltransferase (TIGR01983; EC 2.1.1.64; HMM-score: 13.1) ...
... whose formation is catalyzed by O-methyltransferases that act on phenols, e.g., Catechol-O-methyl transferase (COMT). Many ... natural products in plants, e.g. lignins, are generated via catalysis by caffeoyl-CoA O-methyltransferase. Organic methoxides ...
... is produced by the methylation of L-DOPA by the enzyme catechol-O-methyltransferase. The necessary cofactor for ... 3-O-methyldopa is a major metabolite of L-3,4-dihydroxyphenylalanine (L-DOPA) and is formed by catechol-O-methyltransferase ( ... This process is catalyzed by catechol O-methyltransferase methylates (COMT). The action of the enzyme makes it possible the ... Tai, C. H.; Wu, R. M. (2002). "Catechol-O-methyltransferase and Parkinson's disease". Acta medica Okayama. 56 (1): 1-6. PMID ...
"Inhibition of catechol-O-methyltransferase activity by two novel disubstituted catechols in the rat". European Journal of ... Nitecapone (INN; OR-462) is a drug which acts as a selective inhibitor of the enzyme catechol O-methyl transferase (COMT). It ... Catechol-O-methyltransferase inhibitor F.. Macdonald (1997). Dictionary of Pharmacological Agents. CRC Press. p. 1635. ISBN 978 ...
... is not metabolized by catechol-O-methyltransferase. The plasma half-life measured after oral administration is about ...
... allelic polymorphism of the catechol-O-methyltransferase (COMT) gene; increased adenosine receptor function; increased cortisol ...
It is also a potent catechol O-methyltransferase (COMT) inhibitor. 1,4-Dihydroxyanthraquinone (quinizarin) Alizarin, a related ...
March 2012). "Catechol-O-methyltransferase in complex with substituted 3'-deoxyribose bisubstrate inhibitors". Acta ... Manikumar G, Jin C, Rehder KS (2008). "Convenient Synthesis of Tolcapone, a Selective Catechol‐O‐methyltransferase Inhibitor". ... a novel inhibitor of catechol-O-methyltransferase". British Journal of Clinical Pharmacology. 48 (4): 513-20. doi:10.1046/j. ... potent and reversible nitrocatechol-type inhibitor of the enzyme catechol-O-methyltransferase (COMT). It has demonstrated ...
... as a substrate for catechol-o-methyltransferase". Z. Naturforsch. C (in German). 31 (5-6): 280-284. doi:10.1515/znc-1976-5-611 ... through incubation with rat liver catechol-O-methyltransferase. Umbelliferone "Aesculetin". Sigma-Aldrich. Dey, P. M.; Harborne ...
... is a selective and reversible inhibitor of the enzyme catechol-O-methyltransferase (COMT). When taken together with ... Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). COMT eliminates biologically active ... entacapone stops catechol-O-methyltransferase from breaking down and metabolizing levodopa, resulting in an overall increase of ... catechols present in catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. When ...
A comparison of dopamine agonists and catechol-O-methyltransferase inhibitors in Parkinson's disease. Clinical ...
It can inhibit 2-hydroxy and 4-hydroxyestradiol methylation by catechol-O-methyltransferase. It potently and specifically ...
"A catechol-O-methyltransferase that is essential for auditory function in mice and humans". Proceedings of the National Academy ... which is a transmembrane catechol-O-methyltransferase and is called LRTOMT2, TOMT or COMT2. The COMT2 is essential for auditory ... Leucine rich transmembrane and O-methyltransferase domain containing is a protein that in humans is encoded by the LRTOMT gene ... "Entrez Gene: Leucine rich transmembrane and O-methyltransferase domain containing". Riahi Z, Bonnet C, Zainine R, Louha M, ...
"Genetic polymorphisms of catechol-O-methyltransferase modify the neurobehavioral effects of mercury in children". Journal of ...
In vitro, the meta-hydroxyl group of catechol is methylated by catechol-O-methyltransferase. Four of the five hydroxyl groups ...
"A catechol-O-methyltransferase that is essential for auditory function in mice and humans". Proceedings of the National Academy ...
Gogos JA, Morgan M, Luine V, Santha M, Ogawa S, Pfaff D, Karayiorgou M (August 1998). "Catechol-O-methyltransferase-deficient ...
It is a single nucleotide polymorphism (SNP) in the COMT gene that codes catechol-O-Methyltransferase. The single nucleotide ... "A possible association between the Val158Met polymorphism of the catechol-O-methyl transferase gene and the personality trait ... "An association study of catechol-O-methyltransferase and monoamine oxidase A polymorphisms and personality traits in Koreans". ... "Association of the functional catechol-O-methyltransferase VAL158MET polymorphism with the personality trait of extraversion". ...
4.*Marbach, J.J., and Levitt, M., Catechol_o_Methyl_Transferase Activity in TMJ Patients. J. Dent. Res. 54, 1975. 5.Lipton, J ... 11.*Marbach, J.J., and Levitt, M., Erythrocyte Catechol_o_Methyl_Transferase Activity in Facial Pain Patients. Journal Dental ...
Catechol-O-methyl transferase (COMT) is an enzyme that catalyzes the extraneuronal breakdown of catecholamines. The gene that ...
Catechol O-methyltransferase; PNMT: Phenylethanolamine N-methyltransferase ... tyramine N-methyltransferase in the second, and N-methyl-tyramine-β-hydroxylase in the third.[30][31] This pathway differs from ... and the conversion of octopamine to synephrine by phenylethanolamine N-methyltransferase.[25][30] ...
"Site-specific role of catechol-O-methyltransferase in dopamine overflow within prefrontal cortex and dorsal striatum". The ...
... is a metabolite of norepinephrine created by action of catechol-O-methyl transferase on norepinephrine. It is ...
"Polymorphisms of the serotonin-2A receptor and catechol-O-methyltransferase genes: a study on fibromyalgia susceptibility". ...
"Evidence of epistasis between the catechol-O-methyltransferase and aldehyde dehydrogenase 3B1 genes in paranoid schizophrenia ...
However, the 4-hydroxy group makes it susceptible to metabolism by catechol-O-methyl transferase (COMT). Since it is β2- ...
Leuchter AF, McCracken JT, Hunter AM, Cook IA, Alpert JE (August 2009). "Monoamine oxidase a and catechol-o-methyltransferase ...
"Association between the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism and Alexithymia in Patients with Obsessive- ... levels associated with the Val/Val allele of the Rs4680 polymorphism in the gene that encodes Catechol-O-methyltransferase ( ...
"The dual-state theory of prefrontal cortex dopamine function with relevance to catechol-o-methyltransferase genotypes and ...
The catechol-o-methyl transferase gene (COMT) codes for an enzyme that degrades catecholamine neurotransmitters (DA and NE), ... Tunbridge, E. M. (9 June 2004). "Catechol-O-Methyltransferase Inhibition Improves Set-Shifting Performance and Elevates ...
... (metadrenaline) is a metabolite of epinephrine (adrenaline) created by action of catechol-O-methyl transferase on ...
... kanggo dieliminasi kanti pira-pira prosès kaya ta metilasi kanti enzim catechol-o-methyltransferase, hidroksilasi, oksidasi, ...
The meta-hydroxyl group of catechol is methylated by catechol-O-methyltransferase. Four of the five hydroxyl groups of ...
... allelic polymorphism of the catechol-O-methyltransferase (COMT) gene; increased adenosine receptor function; increased cortisol ...
... followed by methylation of the aromatic ring via catechol-O-methyl transferase. Then hydroxylation of both the aromatic ring ...
... of cellular estrogenic activity based on estrogen receptor-mediated reduction of soluble-form catechol-O-methyltransferase ( ...
Phenylethanolamine N-methyltransferase. catabolism:. *Catechol-O-methyl transferase. *Monoamine oxidase *A. *B ...
... this catechol group undergoes extensive metabolism upon uptake in the human body, for example by catechol-O-methyl transferase ... In many polyphenols the catechol group acts as an electron acceptor and is therefore responsible for the antioxidant activity.[ ...
Barnett, J. H.; Jones, P. B.; Robbins, T. W.; Müller, U. (27 February 2007). "Effects of the catechol-O-methyltransferase ... The low activity polymorphism of Catechol-O-methyltransferase is associated with slight increase in performance on executive ...
... catechol-o-methyl transferase, SK3 and opioid receptor delta-1.[44] Epigenetic modifications, such as DNA methylation, may ...
... which can be further modified by the enzyme phenylethanol N-methyltransferase to obtain epinephrine.[11] Since L-DOPA is the ... Phenylethanolamine N-methyltransferase. catabolism:. *Catechol-O-methyl transferase. *Monoamine oxidase *A. *B ...
... relating to transferase is the discovery of the mechanism of catecholamine breakdown by catechol-O-methyltransferase. This ... N-methyltransferase would be the standard naming convention for the transferase methylamine-glutamate N-methyltransferase, ... a DNA methyltransferase is a transferase that catalyzes the transfer of a methyl group to a DNA acceptor. In practice, many ... where methylamine is the donor, L-glutamate is the acceptor, and methyltransferase is the EC category grouping. This same ...
5-hydroxyindole-O-methyltransferase/Acetylserotonin O-methyltransferase. *Catechol-O-methyl transferase. Homocysteine. *Betaine ...
5-hydroxyindole-O-methyltransferase/Acetylserotonin O-methyltransferase. *Catechol-O-methyl transferase. Homocysteine. *Betaine ... Information about DNA methyltransferases and DNA methylation at epigeneticstation.com. *Data for a DNA methyltransferase (DNMT ... DNMT1 is the most abundant DNA methyltransferase in mammalian cells, and considered to be the key maintenance methyltransferase ... methyltransferases. Classification of all DNA methyltransferases". Gene. 157 (1-2): 3-11. doi:10.1016/0378-1119(94)00783-O. ...
... mandelic acid are formed as a result of metabolism of adrenaline and noradrenaline by monoamine oxidase and catechol-O-methyl transferase ...
In the cytosol, noradrenaline is converted to epinephrine by the enzyme phenylethanolamine N-methyltransferase (PNMT) and ... water-soluble compounds that have a structure made of a catechol group and an amine group. The adrenal glands are responsible ...
Monoamine oxidase and catechol-O-methyl transferase activities in cat nictitating membrane and rat and guinea-pig vas deferens ...
... the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase ...
This has been postulated to be explained by variations of the gene which codes for the enzyme catechol-O-methyl transferase ( ...
"Association between the Catechol-O-Methyltransferase (COMT) Val¹⁵⁸Met Polymorphism and Alexithymia in Patients with Obsessive- ... levels associated with the Val/Val allele of the Rs4680 polymorphism in the gene that encodes Catechol-O-methyltransferase ( ...
Catechol-O-methyl transferase EC 2.1.1.6. *DNA methyltransferase EC 2.1.1.72, EC 2.1.1.113, EC 2.1.1.37 ...
... is known to be metabolized by two main metabolic pathways: (1) O-demethylenation followed by catechol-O-methyltransferase ...
5-hydroxyindole-O-methyltransferase/Acetylserotonin O-methyltransferase. *Catechol-O-methyl transferase. Homocysteine. *Betaine ... Thiopurine methyltransferase or thiopurine S-methyltransferase (TPMT) is an enzyme that in humans is encoded by the TPMT gene. ... methyltransferase activity. • thiopurine S-methyltransferase activity. • S-adenosyl-L-methionine binding. Cellular component. • ... evidence for catalysis by human liver thiol methyltransferase and thiopurine methyltransferase". J. Pharmacol. Exp. Ther. 266 ( ...
Histamine N-methyltransferase inhibitors. آمودیاکین • BW-۳۰۱U • دیفن هیدرامین • هارمالین • Metoprine • کیناکرین • SKF-۹۱٬۴۸۸ • ...
Catechol O-methyl transferase (COMT) inhibitors such as entacapone and tolcapone, which are used in the treatment of ... and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Also, any endogenous or exogenous chemical ...
... can be directly metabolized by catechol-O-methyl transferase to 3-O-methyldopa, and then further to vanillactic acid. ...
Pooley, EC; Fineberg, N; Harrison, PJ (June 2007). "The met(158) allele of catechol-O-methyltransferase (COMT) is associated ... Azzam, A; Mathews, CA (15 November 2003). "Meta-analysis of the association between the catecholamine-O-methyl-transferase gene ...
... a major catecholamine metabolite that is produced by a consecutive action of monoamine oxidase and catechol-O-methyltransferase ...
A catechol-O-methyltransferase (COMT) inhibitor is a drug that inhibits the enzyme catechol-O-methyltransferase. This enzyme ... "Identification of novel flavonoid inhibitor of Catechol-O-Methyltransferase enzyme by molecular screening, quantum mechanics/ ... diarrhea drowsiness urine discoloration dyskinesia Medication Management of Parkinson's disease catechol-O-methyltransferase ...
... and various drugs and substances having a catechol structure. In humans, catechol-O-methyltransferase protein is encoded by the ... Fan JB, Zhang CS, Gu NF, Li XW, Sun WW, Wang HY, Feng GY, St Clair D, He L (January 2005). "Catechol-O-methyltransferase gene ... Fan JB, Zhang CS, Gu NF, Li XW, Sun WW, Wang HY, Feng GY, St Clair D, He L (January 2005). "Catechol-O-methyltransferase gene ... Catechol-O-methyltransferase (COMT; EC 2.1.1.6) is one of several enzymes that degrade catecholamines (such as dopamine, ...
A catechol-O-methyltransferase (COMT) inhibitor is a drug that inhibits the enzyme catechol-O-methyltransferase. This enzyme ... "Identification of novel flavonoid inhibitor of Catechol-O-Methyltransferase enzyme by molecular screening, quantum mechanics/ ... diarrhea drowsiness urine discoloration dyskinesia Medication Management of Parkinsons disease catechol-O-methyltransferase ...
Structural mechanism of S-adenosyl methionine binding to catechol O-methyltransferase.. Tsao D1, Diatchenko L, Dokholyan NV. ... Using catechol O-methyltransferase (COMT) as a model, we perform discrete molecular dynamics and computational docking ... Methyltransferases possess a homologous domain that requires both a divalent metal cation and S-adenosyl-L-methionine (SAM) to ... The proposed mechanism enables a general understanding of how divalent metal cations contribute to methyltransferase function. ...
X-ray Crystal Structure of a Bisubstrate Inhibitor Bound to the Enzyme Catechol-O-methyltransferase: A Dramatic Effect of ... CATECHOL O-METHYLTRANSFERASE, SOLUBLE FORM A 221 Rattus norvegicus EC#: 2.1.1.6 IUBMB Gene Name(s): Comt ...
Effect of catechol-O-methyltransferase Val(108/158)Met polymorphism on antidepressant efficacy of fluvoxamine.. Benedetti F1, ... The catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines, and the COMT Val(108/158)Met polymorphism (rs4680) ...
Purchase Basic Aspects of Catechol-O-Methyltransferase and the Clinical Applications of its Inhibitors, Volume 95 - 1st Edition ... Basic Aspects of Catechol-O-Methyltransferase and the Clinical Applications of its Inhibitors, Volume 95 1st Edition. 0.0 star ... Introductory remarks: Catechol-O-methyltransferase inhibition: an innovative approach to enhance L-dopa therapy in Parkinsons ... Basic Aspects of Catechol-O-Methyltransferase and the Clinical Applications of its Inhibitors ...
Polymorphic Catechol-O-methyltransferase Gene and Breast Cancer Risk. Katja Mitrunen, Nadejda Jourenkova, Vesa Kataja, Matti ... Polymorphic Catechol-O-methyltransferase Gene and Breast Cancer Risk. Katja Mitrunen, Nadejda Jourenkova, Vesa Kataja, Matti ... Polymorphic Catechol-O-methyltransferase Gene and Breast Cancer Risk. Katja Mitrunen, Nadejda Jourenkova, Vesa Kataja, Matti ... Polymorphic Catechol-O-methyltransferase Gene and Breast Cancer Risk Message Subject (Your Name) has forwarded a page to you ...
Inhibitors of Catechol-O-Methyltransferase. Author(s): James C. Barrow. Lieber Institute for Brain Development, 336 John G. ... Keywords:Catechol-O-methyltransferase, COMT, dopamine, L-DOPA, Parkinsons disease, nitrocatechol, MB-COMT, SAM Binding, HPLC, ... Keywords: Catechol-O-methyltransferase, COMT, dopamine, L-DOPA, Parkinsons disease, nitrocatechol, MB-COMT, SAM Binding, HPLC ... Since the identification of Catechol-O-Methyltransferase (COMT) by Axelrod in 1957, many inhibitors of this enzyme have been ...
Keywords: major depressive disorder, duloxetine, catechol-O-methyltransferase, 3-methoxy-4-hydroxyphenylglycol, homovanillic ... and Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene. Subjects and methods: Sixty-four patients and 30 ... Catechol-O-methyltransferase Val158Met genotype and the clinical responses to duloxetine treatment or plasma levels of 3- ... Catechol-O-methyltransferase Val158Met genotype and the clinical responses to duloxetine treatment or plasma levels of 3- ...
PubMed journal article Catechol-O-methyltransferase Val158Met polymorphism (rs4680) is associated with pain in multiple ... AdultAllelesCatechol O-MethyltransferaseFemaleGenetic Predisposition to DiseaseGenotypeHumansMaleMethionineMiddle AgedMultiple ... "Catechol-O-methyltransferase Val158Met Polymorphism (rs4680) Is Associated With Pain in Multiple Sclerosis." The Journal of ... Catechol-O-methyltransferase Val158Met Polymorphism (rs4680) Is Associated With Pain in Multiple Sclerosis. J Pain. 2013;14(12 ...
A case-control study was performed to assess the potential influence of catechol O-methyl transferase (COMT) genotype on the ... Relationship between the Val158Met polymorphism of catechol O-methyl transferase and breast cancer Pharmacogenetics. 2001 Jun; ... A case-control study was performed to assess the potential influence of catechol O-methyl transferase (COMT) genotype on the ...
Lack of Association of Alcohol Dependence and Habitual Smoking With Catechol-O-methyltransferase. Authors. *. Tatiana Foroud,. ... Objective: To test whether variation in the gene encoding the enzyme catechol-O-methyltransferase (COMT), which catalyzes the ... Lack of Association of a Functional Catechol-O-Methyltransferase Gene Polymorphism With Risk of Tobacco Smoking: Results From a ... The lack of association between catechol-O-methyl-transferase Val108/158Met polymorphism and smoking in schizophrenia and ...
Catechol-O-methyltransferase (COMT), an enzyme that is involved in the degradation of catecholamine neurotransmitters (e.g., ... 2005). Catechol-O-methyltransferase (COMT) genotypes and working memory: associations with differing cognitive operations. ... 2004). Functional Analysis of Genetic Variation in Catechol-O-Methyltransferase (COMT): Effects on mRNA, Protein, and Enzyme ... 1996). Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo- ...
COMT (catechol-O-methyltransferase) is an enzyme which inactivates catechols, including the significant neurotransmitters ... Genetic contribution of catechol-o-methyltransferase variants in treatment outcome of low back pain: a prospective genetic ... Catechol-O-methyltransferase (COMT) codes for a protein which is important in catabolic pathways of a number of pain-relevant ... Rakvåg TT, Ross JR, Sato H, Skorpen F, Kaasa S, Klepstad P. Genetic variation in the catechol-O-methyltransferase (COMT) gene ...
Showing Protein Catechol O-methyltransferase (HMDBP00272). IdentificationBiological propertiesGene propertiesProtein properties ... Rutherford K, Le Trong I, Stenkamp RE, Parson WW: Crystal structures of human 108V and 108M catechol O-methyltransferase. J Mol ... Bertocci B, Miggiano V, Da Prada M, Dembic Z, Lahm HW, Malherbe P: Human catechol-O-methyltransferase: cloning and expression ... Ulmanen I, Lundstrom K: Cell-free synthesis of rat and human catechol O-methyltransferase. Insertion of the membrane-bound form ...
No difference in the distribution of the catechol-O-methyltransferase genotypes (H/H, H/L, L/L) and alleles (H, L) was observed ... Catechol-O-methyltransferase, which has a functional genetic polymorphism, plays an important role in dopamine metabolism. The ... Association study of catechol-O-methyltransferase gene polymorphism in Korean male alcoholics. ... Polymerase chain reaction-based genotyping was used to verify the presence of the catechol-O-methyltransferase gene ...
catechol-O-methyltransferase (COMT), Sequence Homology Amino Acid, enzmes. patent number. WO1991011513 A3. language. English. ... Catechol-o-methyltransferase, polypeptide sequences and dna molecule coding therefor. Jalanko, Anu; Kalkkinen, Nisse; Lundström ... catechol-O-methyltransferase (COMT),Sequence Homology Amino Acid,enzmes}, language = {eng}, month = {10}, note = {Patent, ... Catechol-o-methyltransferase, polypeptide sequences and dna molecule coding therefor}, year = {1991}, } ...
Catechol-O-methyltransferase (COMT) metabolizes catecholamines (Männisto and Kaakkola, 1999). The human COMT gene contains a ... Catechol-O-Methyltransferase Inhibition Improves Set-Shifting Performance and Elevates Stimulated Dopamine Release in the Rat ... Catechol-O-Methyltransferase Inhibition Improves Set-Shifting Performance and Elevates Stimulated Dopamine Release in the Rat ... Catechol-O-Methyltransferase Inhibition Improves Set-Shifting Performance and Elevates Stimulated Dopamine Release in the Rat ...
Green Tea Extract and Catechol-O-Methyltransferase Genotype Modify Fasting Serum Insulin and Plasma Adiponectin Concentrations ... stratified by catechol-O-methyltransferase (COMT) genotype. This study was conducted in a subset of 237 overweight and obese ...
Catechol-O-methyltransferase (COMT) plays an essential role in detoxification of catechols by transferring the methyl group ... Catechol-O-methyltransferase: a dual-role player in different breast cancer subtypes?. Autoři. JANÁČOVÁ Lucia FAKTOR Jakub ... Catechol-O-methyltransferase: a dual-role player in different breast cancer subtypes? ...
Catechol-O-methyltransferase (COMT) is a key regulator of pain perception, cognitive function, and affective mood. Three common ... Human Catechol-O-Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure ... Human Catechol-O-Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure ... Human Catechol-O-Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure ...
Catechol-O-methyltransferase genotype and dopamine regulation in the human brain. J Neurosci. 2003;23:2008-2013. [PubMed] ... catechol O-methyl transferase. Hif-1α. hypoxia-inducible factor 1alpha. Iba1. ionized calcium-binding adaptor molecule 1. SMRT ... Gogos JA, Morgan M, Luine V, Santha M, Ogawa S, Pfaff D, Karayiorgou M. Catechol-O-methyltransferase-deficient mice exhibit ... TRAUMATIC BRAIN INJURY STIMULATES HIPPOCAMPAL CATECHOL-O-METHYL TRANSFERASE EXPRESSION IN MICROGLIA. John B. Redell and Pramod ...
By Celina Scott in Catechol methyltransferase April 19, 2017. IL-6 is a secreted cytokine that functions through binding two ... By Celina Scott in Catechol methyltransferase May 3, 2017. Diabetes is a chronic metabolic disease that impacts a substantial ... By Celina Scott in Catechol methyltransferase June 5, 2017. SLAMF9 is an associate from the signaling lymphocyte-activating ... By Celina Scott in Catechol methyltransferase May 21, 2017. Bariatric surgery is now very common & most physicians shall ...
... metabolised by catechol-O-methyltransferase enzyme. The main aim of the study was to ascertain whether the Val158Met catechol-O ... RESULTS: We did not find any significant association between the Val158Met catechol-O-methyltransferase gene polymorphism and ... More attention should also be paid to possible role of the Val158Met catechol-O-methyl-transferase gene polymorphism in ... Hosák A, Serý M, Beranek A, Alda A, Lack of association between the Val158Met catechol-O-methyltransferase gene polymorphism ...
1980) Catechol-O-methyltransferase activity: a determinant of levodopa response. Clin Pharmacol Ther 28:278-286. ... 1994) Catechol-O-methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonian patients. Neurology ... Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma ... Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in ...
Catechol-O-methyltransferase (COMT) is an enzyme involved in the degradation and inactivation of the neurotransmitter dopamine ... Catechol O-Methyltransferase / genetics*. China. Cohort Studies. Genetic Predisposition to Disease. Genotype. Humans. Logistic ... Association of functional catechol O-methyl transferase (COMT) Val108Met polymorphism with smoking severity and age of smoking ... RATIONALE: Catechol-O-methyltransferase (COMT) is an enzyme involved in the degradation and inactivation of the ...
Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is a ubiquitous enzyme that is crucial to the metabolism of carcinogenic ... Characterization and Implications of Estrogenic Down-Regulation of Human Catechol-O-Methyltransferase Gene Transcription Tao ... Characterization and Implications of Estrogenic Down-Regulation of Human Catechol-O-Methyltransferase Gene Transcription Tao ... Characterization and Implications of Estrogenic Down-Regulation of Human Catechol-O-Methyltransferase Gene Transcription Tao ...
Genetic variants of catechol-O-methyltransferase (COMT) gene have previously been shown to be associated with pain sensitivity ... Genetic contribution of catechol-O-methyltransferase variants in treatment outcome of low back pain: a prospective genetic ...
Catechol-O-Methyltransferase (COMT) Pharmacogenetics in the Treatment Response Phenotypes of Major Depressive Disorder (MDD). ... Title:Catechol-O-Methyltransferase (COMT) Pharmacogenetics in the Treatment Response Phenotypes of Major Depressive Disorder ( ... Neslihan Aygun Kocabas, "Catechol-O-Methyltransferase (COMT) Pharmacogenetics in the Treatment Response Phenotypes of Major ... Keywords:COMT gene, pharmacogenetics, antidepressant, treatment response, snp, Catechol O Methyl Transferase, Major Depressive ...
... we hypothesized that genetic variation in catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, would ... Catechol-O-Methyltransferase moderates effect of stress mindset on affect and cognition. Crum, Alia J.; Akinola, Modupe; ... we hypothesized that genetic variation in catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, would ...
  • Effect of catechol-O-methyltransferase Val(108/158)Met polymorphism on antidepressant efficacy of fluvoxamine. (nih.gov)
  • The catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines, and the COMT Val(108/158)Met polymorphism (rs4680) influences the enzyme activity. (nih.gov)
  • This study investigated the relationships among the plasma levels of catecholamine metabolites, the clinical response to duloxetine treatment, and Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene. (dovepress.com)
  • 1996). Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome. (salimetrics.com)
  • Catechol-O-methyltransferase, which has a functional genetic polymorphism, plays an important role in dopamine metabolism. (ovid.com)
  • The study analyzed the association between the catechol-O-methyltransferase gene polymorphism and alcohol dependence in the Korean population. (ovid.com)
  • Polymerase chain reaction-based genotyping was used to verify the presence of the catechol-O-methyltransferase gene polymorphism. (ovid.com)
  • This suggests that the catechol-O-methyltransferase gene polymorphism is not associated with the development of alcohol dependence, but may affect the susceptibility to a clinical heterogeneity of alcohol dependence, at least in the Korean population. (ovid.com)
  • Association of functional catechol O-methyl transferase (COMT) Val108Met polymorphism with smoking severity and age of smoking initiation in Chinese male smokers. (biomedsearch.com)
  • Background: The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism, Val158Met, which has been linked to anxiety and depression, but previous results are not conclusive. (ebscohost.com)
  • No association between catechol-o-methyltransferase Val108/158Met polymorphism and schizophrenia or its clinical symptomatology in a Mexican population. (ebscohost.com)
  • Aims To study the possible association of catechol-O-methyltransferase ( COMT) Val158Met polymorphism with multiple and solitary uterine leiomyomas (ULs) and to check whether the COMT Val/Val genotype is associated with MED12 exon 2 mutations in fibroids. (bmj.com)
  • The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been found to affect fear extinction and might play a role in the etiology of anxiety disorders. (lancs.ac.uk)
  • Modulation of brain structure by catechol-O-methyltransferase Val(158) Met polymorphism in chronic cannabis users. (nispa.nl)
  • Recent work focusing on the relationship between brain structure and the catechol-O-methyltransferase (COMT) gene polymorphism suggests that functional COMT variants may affect brain volume in healthy individuals and in schizophrenia patients. (nispa.nl)
  • Catechol-o-methyltransferase (COMT) alters extracellular dopamine levels in PFC, and its gene contains a functional polymorphism (Val(158)Met) that has been associated with variation in PFC function. (ox.ac.uk)
  • We have previously reported that NRG1-stimulated migration of B lymphoblasts is PI3K-AKT1dependent and impaired in patients with schizophrenia and significantly linked to the catechol-o-methyltransferase (COMT) Val108/158Met functional polymorphism. (ox.ac.uk)
  • A functional single nucleotide polymorphism (a common normal variant) of the gene for catechol-O-methyl transferase has been shown to affect cognitive tasks broadly related to executive function, such as set shifting, response inhibition, abstract thought, and the acquisition of rules or task structure. (chemeurope.com)
  • Diverse phenotypic associations with the catechol-O-methyltransferase (COMT) Val 158 Met polymorphism have been reported. (elsevier.com)
  • Most studies have focused on the effects of a particular common variation (polymorphism) in catechol-O-methyltransferase. (medlineplus.gov)
  • Enzyme analysis of the conversion ratio of catechol to O-alkylated guaiacol confirmed the inhibitory effect of oleacein on human COMT, which remained unaltered when tested against the protein version encoded by the functional Val158 Met polymorphism of the COMT gene. (qxmd.com)
  • We examined 483 Finnish breast cancer cases and 482 population controls to determine the potential effect of catechol- O -methyltransferase ( COMT ) genotype in individual susceptibility to breast cancer. (aacrjournals.org)
  • A case-control study was performed to assess the potential influence of catechol O-methyl transferase (COMT) genotype on the risk of breast cancer in Korean women. (nih.gov)
  • The Minnesota Green Tea Trial was a 12-mo randomized, double-blind, placebo-controlled clinical trial of 937 healthy postmenopausal women assigned to either decaffeinated GTE (1315 mg total catechins/d) or a placebo, stratified by catechol-O-methyltransferase (COMT) genotype. (nih.gov)
  • Structural equation modeling was applied to data on 704 Norwegian children to test whether the catechol-O-methyltransferase Val158Met genotype moderates the effect of disorganized attachment, which was measured dimensionally at 4 years of age using the Manchester Child Attachment Story Task, on changes in aggressive behavior and social competence from ages 4 to 6. (samforsk.no)
  • Allelic and genotype frequencies of catechol-O-methyltransferase (Val158Met) and CYP2D6*10 (Pro34Ser) single nucleotide polymorphisms in the Philippines. (althotas.com)
  • A hospital-based cross-sectional study was conducted to determine the allelic and genotype frequencies in the genes encoding for catechol-O-methyltransferase and CYP2D6*10 among healthy volunteers and patients clinically diagnosed with cancer pain. (althotas.com)
  • Genotype status of the dopamine-related catechol-O-methyltransferase (COMT) gene corresponds with desirability of 'unhealthy' foods. (berkeley.edu)
  • Genotype status of the dopamine-related catechol-O-methyltransferase (COMT) gene has been shown to influence dopamine levels, with greater COMT enzymatic activity in val/val individuals corresponding to greater degradation of dopamine. (berkeley.edu)
  • The influence of Catechol-O-Methyltransferase Val158Met on fear of pain and placebo analgesia. (painresearchforum.org)
  • Fundist hefur breytileiki í einum basa (Val158Met, rs4680) í erfðaefninu á milli einstaklinga, sem veldur því að þegar A samsæta er til staðar er COMT ensímið mun lengur að brjóta niður dópamín en þegar G samsæta er til staðar7. (lsh.is)
  • Identification of major metabolites of the catechol-O-methyltransferase inhibitor entacapone in rats and humans. (aspetjournals.org)
  • Metabolites of entacapone [(E)-2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)propenamide++ +], a potent inhibitor of catechol-O-methyltransferase, were isolated from human and rat urine. (aspetjournals.org)
  • The nitro group of entacapone seems to hinder methylation of the catechol hydroxyls in man, because no methylation products were detected. (aspetjournals.org)
  • The inhibition of soluble catechol- O -methyltransferase (S-COMT) in red blood cells (RBCs) by entacapone, and the pharmacokinetics of entacapone after single oral (5-800 mg) and IV (25 mg) doses have been examined in an open study in 12 healthy young male volunteers. (springer.com)
  • Karlsson M, Wikberg T (1992) Liquid chromatographic determination of a new catechol-O-methyltransferase inhibitor, entacapone, and its Z-isomer in human plasma and urine. (springer.com)
  • Keränen T, Gordin A, Harjola V-P, Karlsson M, Korpela K, Pentikäinen PJ, Rita H, Seppälä L, Wikberg T (1993) The effect of catechol-O-methyltransferase inhibition by entacapone, on the pharmacokinetics and metabolism of levodopa in healthy volunteers. (springer.com)
  • Grünig, David;Felser, Andrea;Duthaler, Urs;Bouitbir, Jamal;Krähenbühl, Stephan 2018-04-23 00:00:00 Abstract Tolcapone and entacapone are catechol-O-methyltransferase inhibitors used in patients with Parkinson's disease. (deepdyve.com)
  • COMT inhibitors, HepaRG cells, fatty acid metabolism, long-chain acyl-CoA synthetase, VLDL secretion Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors used for the treatment of patients with Parkinson's disease. (deepdyve.com)
  • L-DOPA Entacapone Tolcapone Opicapone Catechol-O-methyl transferase Parkinson's disease Parkinson's Disease and movement disorders. (wikipedia.org)
  • Entacapone is an inhibitor of catechol-O-methyltransferase (COMT), used in the treatment of Parkinson's disease as an adjunct to levodopa and carbidopa therapy. (rxlist.com)
  • Entacapone is a selective and reversible inhibitor of catechol- O -methyltransferase (COMT). (nih.gov)
  • Studies in healthy volunteers have shown that entacapone reversibly inhibits human erythrocyte catechol- O -methyltransferase (COMT) activity after oral administration. (nih.gov)
  • Carbidopa, levodopa and entacapone tablets, a combination drug consisting of levodopa (aromatic amino acid), carbidopa (aromatic amino acid decarboxylation inhibitor), and entacapone (catechol-O-methyltransferase (COMT) inhibitor) is indicated for the treatment of Parkinson's disease. (nih.gov)
  • Volume 95 of International Review of Neurobiology focuses on Catechol-O-methyltransferase inhibition, and its clinical application in relation to Parkinson's disease. (elsevier.com)
  • Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa. (bmj.com)
  • We investigated the effects of peripheral catechol-O-methyltransferase (COMT) inhibition, by the non-toxic drug nitecapone on the metabolism of 6-[ 18 F]fluoro-l-dihydroxyphenylalanine (6FD) and on its positron emission tomography (PET) imaging in non-human primates. (elsevier.com)
  • Kopin, Irwin J. / 6-[18F]Fluoro-l-dihydroxyphenylalanine metabolism and positron emission tomography after catechol-O-methyltransferase inhibition in normal and hemiparkinsonian monkeys . (elsevier.com)
  • Despite the addition of a peripheral decarboxylase inhibitor, levodopa is extensively metabolised in the periphery to 3-O-methyldopa (3-OMD) by catechol-O-methyltransferase (COMT). (bmj.com)
  • Catechol O-methyltransferase inhibitor was associated with up to a 65% increase in JC410 cell number and a maximal 5.6-fold increase in p450SCC-luciferase activity at 20 μmol/L. Dihydrotestosterone, insulin, and ATRA all induced a dose-dependent increase in COMTP1-luciferase transactivation, as well as up-regulated COMT messenger RNA expression in granulosa cells. (elsevier.com)
  • Catechol O-methyltransferase product, 2-ME 2 , decreased, whereas COMT inhibitor increased granulosa cell proliferation and steroidogenesis. (elsevier.com)
  • Catechol-O-methyltransferase (COMT) polymorphisms predict treatment response in electroconvulsive therapy. (ebscohost.com)
  • Association between catechol-O-methyl transferase gene polymorphisms and fibromyalgia in a Korean population: A case-control study. (painresearchforum.org)
  • Catechol-O-methyltransferase (COMT) gene polymorphisms are associated with baseline disability but not long-term treatment outcome in patients with chronic low back pain. (ox.ac.uk)
  • Polymorphisms in the catechol-O-methyltransferase (COMT) gene influence plasma total homocysteine levels. (ox.ac.uk)
  • We investigated whether functional polymorphisms in catechol-O-methyltransferase (COMT) influence tHcy, since COMT activity produces S-adenosylhomocysteine (SAH), a homocysteine precursor. (ox.ac.uk)
  • They are mainly inactivated by COMT, 3 a Phase II enzyme that methylates catechol estrogens to less polar monomethyl ethers, which can then be excreted. (aacrjournals.org)
  • Our data suggest, that the CYP1B1 Ser allele may decrease endometrial cancer risk by altering the production of catechol estrogens. (cdc.gov)
  • The enzyme COMT is expressed in several tissues and degrades not only dopamine but also other catecholamines and sex steroids, like catechol estrogens and dietary polyphenols. (biomedcentral.com)
  • Catechol-O-methyltransferase (COMT) is involved in phase II (conjugative) metabolism of catecholamines and catechol drugs, such as dopamine, as well as the catechol-estrogens. (testcatalog.org)
  • Estradiol can be hydroxylated forming the catechol estrogens 2-hydroxyestradiol and 4-hydroxyestradiol. (testcatalog.org)
  • This relationship led us to postulate that oxidation of the carcinogenic 4-hydroxy catechol estrogens (CE) of estrone (E 1 ) and estradiol (E 2 ) to catechol estrogen-3,4-quinones (CE-3, 4-Q) results in electrophilic intermediates that covalently bind to DNA to form depurinating adducts. (pnas.org)
  • This relationship led us to postulate that oxidation of catechol estrogens (CE) to CE quinones (CE-Q) results in electrophilic intermediates that also covalently bind to DNA and form depurinating adducts. (pnas.org)
  • misc{d359f84f-dce1-45b6-b22f-f3eac7b75b3d, abstract = {A novel isolation procedure was developed that allowed the purification of rat liver and human placenta catechol-O-methyltransferase (EC 2.1.1.6, COMT) enzyme from rat and human sources to a degree sufficient to allow the amino acid sequencing of the enzyme. (lu.se)
  • Catechol- O -methyltransferase (COMT) metabolizes catecholamines ( Männisto and Kaakkola, 1999 ). (jneurosci.org)
  • Of particular interest was catechol-O-methyl transferase (COMT), an enzyme involved in metabolizing catecholamines released following neuronal activity. (pubmedcentralcanada.ca)
  • After validating altered expression of representative candidates by western blot analysis, we subsequently targeted catechol-O-methyl transferase (COMT), an enzyme involved in the metabolism of the catecholamines dopamine and norepinephrine, for a more extensive characterization. (pubmedcentralcanada.ca)
  • Given the previously established role of catecholamines in both placebo effects and stress, we hypothesized that genetic variation in catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, would moderate responses to an intervention intended to alter participants' mindsets about stress. (columbia.edu)
  • The gene coding for catecol-o-methyltransferase (COMT), participant in the metabolism of catecholamines, has long been implicated as a candidate gene for schizophrenia. (ebscohost.com)
  • Catechol-O-Methyltransferase (COMT) is an enzyme that inactivates catecholamines, such as epinephrine, norepinephrine and dopamine. (genelex.com)
  • Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. (hmdb.ca)
  • In this study, we characterized the enzymology of cytosolic catechol- O -methyltransferase (COMT)-catalyzed methylation of EGCG and EGC in humans, mice, and rats. (aspetjournals.org)
  • Specifically, membrane-bound catechol- O -methyltransferase (MBCOMT) is an integral membrane protein that catalyzes the methylation of catechol substrates and has been linked to several diseases such as Parkinson's disease and Schizophrenia. (biomedcentral.com)
  • NF-κB (a protein involved in inflammation) is a known methylation target of the methyltransferase SETD6, which turns off NF-κB signaling by inhibiting of one of its subunits, RelA. (wikipedia.org)
  • 3-O-methyldopa is produced by the methylation of L-DOPA by the enzyme catechol-O-methyltransferase. (wikipedia.org)
  • Catechol-containing polyphenols present in coffee and tea, while serving as excellent substrates for catechol-O-methyltransferase (COMT)-catalyzed O-methylation, can also operate as COMT inhibitors. (qxmd.com)
  • Catechol-O-methyltransferase (COMT) plays an important role in normal brain function and has been implicated in human disorders, such as Parkinson's disease. (bertin-bioreagent.com)
  • Catechol O-methyltransferase (COMT) inhibitors are valuable co-adjuvant drugs in the clinical management of Parkinson's disease (PD), and recent data also suggest therapeutic benefits in other neurological disorders associated with dopamine depletion. (qxmd.com)
  • Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. (wikipedia.org)
  • Methyltransferases can also be grouped as different types utilizing different substrates in methyl transfer reactions. (wikipedia.org)
  • Lysine methyltransferases and Arginine methyltransferases are unique classes of enzymes, but both bind SAM as a methyl donor for their histone substrates. (wikipedia.org)
  • Any compound having a catechol structure, like catecholestrogens and catechol-containing flavonoids, are substrates of COMT. (chemeurope.com)
  • Using S-adenosyl-L-methionine (SAM) as a methyl donor, COMT methylates catechol substrates, w. (bertin-bioreagent.com)
  • COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. (nih.gov)
  • The rat and human recombinant soluble and membrane-bound catechol O-methyltransferase (S- and MB-COMT, respectively) were expressed using mammalian and baculovirus vectors. (lu.se)
  • The longer form, called membrane-bound catechol-O-methyltransferase (MB-COMT), is chiefly produced by nerve cells in the brain. (medlineplus.gov)
  • Other tissues, including the liver, kidneys, and blood, produce a shorter form of the enzyme called soluble catechol-O-methyltransferase (S-COMT). (medlineplus.gov)
  • The objectives of this study were to determine (1) the effects of dose and drug absorption on pathways of biotransformation of L-DOPA in Parkinsonian patients treated with Sinemet, and (2) the extent to which genetically-determined variations in the activities of erythrocyte catechol O-methyltransferase and/or platelet phenol sulfotransferase might be reflected in individual differences in L-DOPA metabolism. (elsevier.com)
  • No difference in the distribution of the catechol-O-methyltransferase genotypes (H/H, H/L, L/L) and alleles (H, L) was observed between the patients and the controls. (ovid.com)
  • Catechol- O -methyl transferase is involved in the inactivation of the catecholamine neurotransmitters ( dopamine , epinephrine , and norepinephrine ). (chemeurope.com)
  • Catechol O-methyltransferase (COMT) plays an important role for clearance of high catecholamine levels. (elsevier.com)
  • COMT (catechol-O-methyltransferase) is an enzyme which inactivates catechols, including the significant neurotransmitters dopamine, noradrenaline and adrenaline [ 9 ]. (medsci.org)
  • Catechol-O-methyltransferase (COMT) inactivates norepinephrine and dopamine via methyl conjugation, and a G-A transition in the COMT gene (rs4680) influences the enzyme activity. (elsevier.com)
  • 2004). Functional Analysis of Genetic Variation in Catechol-O-Methyltransferase (COMT): Effects on mRNA, Protein, and Enzyme Activity in Postmortem Human Brain. (salimetrics.com)
  • Expression of multiple catechol-o-methyltransferase (COMT) mRNA variants in human brain. (ox.ac.uk)
  • Catechol-O-methyltransferase (COMT Val 158 Met) has been implicated in both depression and cardiovascular disease. (biomedcentral.com)
  • Histone methyltransferases are critical for genetic regulation at the epigenetic level. (wikipedia.org)
  • Objective: To investigate the regulation of catechol O-methyltransferase (COMT) expression in granulosa cells and assess potential effects of 2-methoxyestradiol (2-ME 2 ) and COMT inhibitors on granulosa cell steroidogenesis and proliferation. (elsevier.com)
  • A loss of one copy of the COMT gene in each cell leads to abnormal regulation of catechol-O-methyltransferase levels in the brain. (medlineplus.gov)
  • Epistatic and functional interactions of catechol-o-methyltransferase (COMT) and AKT1 on neuregulin1-ErbB signaling in cell models. (ox.ac.uk)
  • Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) are two key enzymes in the estrogen metabolism pathway that result in the hydroxylation and conjugation of estradiol, respectively. (cdc.gov)
  • The effects of estrogen and progesterone on the expression of estrogen-metabolizing enzymes such as catechol-O-methyl transferase (COMT) are not known. (elsevier.com)
  • 2005). Catechol-O-methyltransferase (COMT) genotypes and working memory: associations with differing cognitive operations. (salimetrics.com)
  • Catechol-o-methyltransferase enzyme activity and protein expression in human prefrontal cortex across the postnatal lifespan. (ox.ac.uk)
  • These types include protein methyltransferases, DNA/RNA methyltransferases, natural product methyltransferases, and non-SAM dependent methyltransferases. (wikipedia.org)
  • COMTD1 (Catechol-O-Methyltransferase Domain Containing 1) is a Protein Coding gene. (genecards.org)
  • Structural mechanism of S-adenosyl methionine binding to catechol O-methyltransferase. (nih.gov)
  • Methyltransferases possess a homologous domain that requires both a divalent metal cation and S-adenosyl-L-methionine (SAM) to catalyze its reactions. (nih.gov)
  • Catechol-O-methyltransferase (COMT) plays an essential role in detoxification of catechols by transferring the methyl group from S-adenosyl-L-methionine to the substrate. (muni.cz)
  • The most common class of methyltransferases is class I, all of which contain a Rossmann fold for binding S-Adenosyl methionine (SAM). (wikipedia.org)
  • Oleacein could be superimposed onto the catechol-binding site of COMT, maintaining the interactions with the atomic positions involved in methyl transfer from the S-adenosyl-L-methionine cofactor. (qxmd.com)
  • This review summarizes the major classes of COMT inhibitors, from early catechol and pyrogallol variants to bisubstrate inhibitors. (eurekaselect.com)
  • Genetic variants of catechol-O-methyltransferase (COMT) gene have previously been shown to be associated with pain sensitivity and pain medication. (uio.no)
  • Catechol- O -methyltransferase (COMT) is a key regulator of pain perception, cognitive function, and affective mood. (sciencemag.org)
  • Catechol-O-methyltransferase (COMT) modulates dopamine in the prefrontal cortex (PFC) and influences PFC dopamine-dependent cognitive task performance. (ox.ac.uk)
  • Many clinical and genomic association studies suggested that the catechol-Omethyltransferase (COMT) gene region was an important genetic locus for psychiatric disorders, because of the proposed relationship between its function in catecholaminergic neurotransmission and individual response to antidepressants, and vulnerability to psychiatric disorders. (eurekaselect.com)
  • Distribution and functions of catechol-O-methyltransferase proteins: do recent findings change the picture? (elsevier.com)
  • Moreover, we verified that recombinant Cmt proteins exhibit catechol O-methyltransferase activity. (elsevier.com)
  • COMT (Catechol-O-methyltransferase) inhibitors enhances levodopa treatment as they inhibit levodopa's peripheral metabolism, thereby enhancing its bioavailability. (holisticonline.com)
  • Catechol-o-methyltransferase (COMT) is important for modulating dopamine levels, prefrontal cortex (PFC) function, and several psychiatric phenotypes. (ox.ac.uk)
  • Catechol-O-methyltransferase is particularly important in an area at the front of the brain called the prefrontal cortex, which organizes and coordinates information from other parts of the brain. (medlineplus.gov)
  • The change affects the stability and activity of catechol-O-methyltransferase, which alters the enzyme's ability to break down neurotransmitters in the prefrontal cortex. (medlineplus.gov)
  • Catechol-O-methyltransferase (COMT) influences the connectivity of the prefrontal cortex at rest. (ox.ac.uk)
  • Neslihan Aygun Kocabas, "Catechol-O-Methyltransferase (COMT) Pharmacogenetics in the Treatment Response Phenotypes of Major Depressive Disorder (MDD)", CNS & Neurological Disorders - Drug Targets (2012) 11: 264. (eurekaselect.com)
  • RATIONALE: Catechol-O-methyltransferase (COMT) is an enzyme involved in the degradation and inactivation of the neurotransmitter dopamine, which is important in mediating drug reward such as nicotine in tobacco smoke. (biomedsearch.com)
  • 1992). Chromosomal mapping of the human catechol-O-methyltransferase gene to 22q11.1--q11.2. (salimetrics.com)
  • A novel isolation procedure was developed that allowed the purification of rat liver and human placenta catechol-O-methyltransferase (EC 2.1.1.6, COMT) enzyme from rat and human sources to a degree sufficient to allow the amino acid sequencing of the enzyme. (lu.se)
  • Ball P, Knuppen R, Breuer H (1971) Purification and properties of catechol-O-methyltransferase of human liver. (springer.com)
  • We found that a homolog of human catechol O-methyltransferase 2 (COMT2) is highly upregulated in S. pombe cells exposed to alkaline conditions. (elsevier.com)
  • In the brain, catechol-O-methyltransferase helps break down certain chemical messengers called neurotransmitters. (medlineplus.gov)
  • Catechol-O-methyltransferase helps maintain appropriate levels of these neurotransmitters in this part of the brain. (medlineplus.gov)
  • Kaakkola S, Wurtman R (1993) Effects of catechol-O-methyltransferase inhibitors and 1-3, 4-dihydroxyphenylalanine with or without carbidopa on extracellular dopamine in rat striatum. (springer.com)
  • Natural product methyltransferases provide a variety of inputs into metabolic pathways, including the availability of cofactors, signalling molecules, and metabolites. (wikipedia.org)
  • Guldberg HC, Marsden CA (1975) Catechol-O-methyltransferase: Pharmacological aspects and physiological role. (springer.com)
  • COMT transfers a donor methyl-group from S-adenosylmethionine to acceptor hydroxy groups on catechol structures (aromatic ring structures with vicinal hydroxy-groups). (testcatalog.org)
  • The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. (nih.gov)