Read by QxMD icon Read

COMT methylation

Shekhar Dethe, M Deepak, Amit Agarwal
BACKGROUND: Bacopa monnieri (L.) Wettst., commonly known as Brahmi, is renowned in Indian traditional system for its potent memory enhancing activity, which has been validated by various scientific studies. OBJECTIVE: The objective of this study was to understand the molecular mechanism of memory enhancing activity of BacoMind(®) (BM), a standardized extract of B. monnieri. MATERIALS AND METHODS: BM was screened in vitro in a panel of cell-free and receptor-transfected cell assays...
July 2016: Pharmacognosy Magazine
Shabnam Nohesara, Mohammad Ghadirivasfi, Mahmood Barati, Mohammad-Reza Ghasemzadeh, Samira Narimani, Zohreh Mousavi-Behbahani, Mohammadtaghi Joghataei, Mansoureh Soleimani, Mozhgan Taban, Soraya Mehrabi, Sam Thiagalingam, Hamid Mostafavi Abdolmaleky
Methamphetamine, one of the most frequently used illicit drugs worldwide, can induce psychosis in a large fraction of abusers and it is becoming a major problem for the health care institutions. There is some evidence that genetic and epigenetic factors may play roles in methamphetamine psychosis. In this study, we examined methamphetamine-induced epigenetic and expression changes of several key genes involved in psychosis. RNA and DNA extracted from the saliva samples of patients with methamphetamine dependency with and without psychosis as well as control subjects (each group 25) were analyzed for expression and promoter DNA methylation status of DRD1, DRD2, DRD3, DRD4, MB-COMT, GAD1, and AKT1 using qRT-PCR and q-MSP, respectively...
October 18, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Heather J Kulik, Jianyu Zhang, Judith P Klinman, Todd J Martínez
Hybrid quantum mechanical-molecular mechanical (QM/MM) simulations are widely used in studies of enzymatic catalysis. Until recently, it has been cost prohibitive to determine the asymptotic limit of key energetic and structural properties with respect to increasingly large QM regions. Leveraging recent advances in electronic structure efficiency and accuracy, we investigate catalytic properties in catechol O-methyltransferase, a representative example of a methyltransferase critical to human health. Using QM regions ranging in size from reactants-only (64 atoms) to nearly one-third of the entire protein (940 atoms), we show that properties such as the activation energy approach within chemical accuracy of the large-QM asymptotic limits rather slowly, requiring approximately 500-600 atoms if the QM residues are chosen simply by distance from the substrate...
October 5, 2016: Journal of Physical Chemistry. B
Christian Lerner, Roland Jakob-Roetne, Bernd Buettelmann, Andreas Ehler, Markus Rudolph, Rosa María Rodríguez Sarmiento
A fragment screening approach designed to target specifically the S-adenosyl-l-methionine pocket of catechol O-methyl transferase allowed the identification of structurally related fragments of high ligand efficiency and with activity on the described orthogonal assays. By use of a reliable enzymatic assay together with X-ray crystallography as guidance, a series of fragment modifications revealed an SAR and, after several expansions, potent lead compounds could be obtained. For the first time nonphenolic and small low nanomolar potent, SAM competitive COMT inhibitors are reported...
October 14, 2016: Journal of Medicinal Chemistry
Colleen P Franconi, Donna McDonald-McGinn, Elaine H Zackai, Meghan A McNamara, Harold Salmons, Edward Moss, Raquel E Gur, Marcella Devoto, Beverly S Emanuel
22q11.2 Deletion Syndrome (22q11DS) is a multisystem disorder caused by a hemizygous deletion within 22q11.2. Patients with the deletion display a wide range of cognitive deficits. The gene catechol-O-methyl-transferase (COMT) resides in the typically deleted region of 22q11.2 and is rendered hemizygous in individuals affected by the 22q11DS. COMT is a critical enzyme in the degradation of catecholamine neurotransmitters in the brain. A functional polymorphism, Val(158) Met, has been associated with a variety of neurocognitive outcomes...
September 13, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Niladri Patra, Efthymios I Ioannidis, Heather J Kulik
Catechol O-methyltransferase (COMT) is a SAM- and Mg2+-dependent methyltransferase that regulates neurotransmitters through methylation. Simulations and experiments have identified divergent catecholamine substrate orientations in the COMT active site: molecular dynamics simulations have favored a monodentate coordination of catecholate substrates to the active site Mg2+, and crystal structures instead preserve bidentate coordination along with short (2.65 Å) methyl donor-acceptor distances. We carry out longer dynamics (up to 350 ns) to quantify interconversion between bidentate and monodentate binding poses...
2016: PloS One
Garima Jindal, Arieh Warshel
Although QM/MM calculations are the primary current tool for modeling enzymatic reactions, the reliability of such calculations can be limited by the size of the QM region. Thus, we examine in this work the dependence of QM/MM calculations on the size of the QM region, using the reaction of catechol-O-methyl transferase (COMT) as a test case. Our study focuses on the effect of adding residues to the QM region on the activation free energy, obtained with extensive QM/MM sampling. It is found that the sensitivity of the activation barrier to the size of the QM is rather limited, while the dependence of the reaction free energy is somewhat larger...
September 22, 2016: Journal of Physical Chemistry. B
Miklós Poór, Zita Zrínyi, Tamás Kőszegi
Dietary flavonoids are abundant in the Plant Kingdom and they are extensively studied because of their manifold pharmacological activities. Recent studies highlighted that cell cycle arrest plays a key role in their antiproliferative effect in different tumor cells. However, structure-activity relationship of flavonoids is poorly characterized. In our study the influence of 18 flavonoid aglycones (as well as two metabolites) on cell cycle distribution was investigated. Since flavonoids are extensively metabolized by liver cells, HepG2 tumor cell line was applied, considering the potential metabolic activation/inactivation of flavonoids...
August 11, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Bilge Kocer, Hayat Guven, Selim Selcuk Comoglu
Plasma homocysteine (Hcy) levels may increase in levodopa-treated patients with Parkinson's disease (PD) as a consequence of levodopa methylation via catechol-O-methyltransferase (COMT). Results from previous studies that assessed the effect of COMT inhibitors on levodopa-induced hyperhomocysteinemia are conflicting. We aimed to evaluate the effects of levodopa and entacapone on plasma Hcy levels. A hundred PD patients were enrolled to the study and divided into three treatment groups (group I: levodopa and/or dopamine agonists; group II: levodopa, entacapone, and/or a dopamine agonist; and group III: dopamine agonist alone)...
2016: BioMed Research International
Zhi Li, Beate W Hygen, Keith F Widaman, Turid S Berg-Nielsen, Lars Wichstrøm, Jay Belsky
Why is disorganized attachment associated with punitive-controlling behavior in some, but caregiving-controlling in others? Hygen et al. (2014) proposed that variation in the Catechol-O-methyl transferase(COMT) Val158Met genotype explains this variation, providing preliminary data to this effect. We offer a conceptual replication, analyzing data on 560 children (males: 275) drawn from the NICHD Study of Early Child Care and Youth Development. As predicted, competitive model-fitting indicated that disorganized infants carrying Met alleles engage in more positive behavior and less negative behavior than other children at age 5 and 11, with the reverse true of Val/Val homozygotes, seemingly consistent with caregiving-controlling and punitive-controlling styles, respectively, but only in the case of maternal and not teacher reports, thereby confirmating a relationship-specific hypothesis...
2016: Frontiers in Psychology
Masato Asanuma, Ikuko Miyazaki
BACKGROUND: We evaluated the effects of 3-O-methyldopa (3-OMD), a metabolite of L-DOPA which is formed by catechol-O-methyltransferase (COMT), on the uptake, metabolism, and neuroprotective effects of L-DOPA in striatal astrocytes. We examined changes in the numbers of dopaminergic neurons after treatment with L-DOPA and 3-OMD or entacapone, a peripheral COMT inhibitor, using primary cultured mesencephalic neurons and striatal astrocytes. RESULTS: The number of tyrosine hydroxylase-positive dopaminergic neurons was not affected by L-DOPA treatment in mesencephalic neurons alone...
2016: BMC Neuroscience
Renata A N Pertile, Xiaoying Cui, Darryl W Eyles
Vitamin D regulates multiple factors including those involved in the ontogeny of dopaminergic systems. It has been shown that in neonatal rats maternally deprived of vitamin D, dopamine (DA) turnover is decreased with associated reductions in one catabolic enzyme, catechol-o-methyl transferase (COMT). To directly examine this signaling relationship, in the present study we have over-expressed the vitamin D receptor (VDR) in neuroblastoma SH-SY5Y cells in order to examine the mechanisms by which the active vitamin D hormone, 1,25(OH)2D3, via its receptor VDR, affects DA production and turnover...
October 1, 2016: Neuroscience
Renee Cockerham, Shaolin Liu, Roger Cachope, Emi Kiyokage, Joseph F Cheer, Michael T Shipley, Adam C Puche
UNLABELLED: The efficacy of neurotransmission depends on multiple factors, including presynaptic vesicular release of transmitter, postsynaptic receptor populations and clearance/inactivation of the transmitter. In the olfactory bulb (OB), short axon cells (SACs) form an interglomerular circuit that uses GABA and dopamine (DA) as cotransmitters. Selective optical activation of SACs causes GABA and DA co-release, resulting in a fast, postsynaptic GABA inhibitory response and a slower G-protein-coupled DA rebound excitation...
July 20, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Si-Cheng Liang, Guang-Bo Ge, Yang-Liu Xia, Dong Pei-Pei, Wang Ping, Xiao-Yi Qi, Tu Cai-Xia, Yang Ling
1. Finding and developing inhibitors of catechol-O-methyltransferase (COMT) from natural products is highly recommended. Daphnetin, a naturally occurring catechol from the family thymelaeaceae, has a chemical structure similar to several potent COMT inhibitors reported previously. Here the potential of daphnetin and its Phase II metabolites as inhibitors of COMT was investigated with human liver cytosol (HLC). 2. Daphnetin and its methylated metabolite (8-O-methyldaphnetin) were found to inhibit COMT-mediated dopamine O-methylation in a dose-dependent manner...
July 20, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Esther D A van Duin, Liesbet Goossens, Dennis Hernaus, Fabiana da Silva Alves, Nicole Schmitz, Koen Schruers, Therese van Amelsvoort
BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic neurotransmission in 22q11DS, which may contribute to the increased vulnerability for psychosis. A dysfunctional motivational reward system is considered one of the salient features in psychosis and thought to be related to abnormal dopaminergic neurotransmission...
2016: Journal of Neurodevelopmental Disorders
Yu-Hsiang Liao, Hsin-Jung Lee, Wei-Jan Huang, Pi-Chuan Fan, Lih-Chu Chiou
RATIONALE: Hispidulin is a flavonoid we isolated from Clerodendrum inerme, an herb that effectively remitted a case of intractable motor tic disorders. Hispidulin was shown to be a positive allosteric modulator (PAM) of GABAA receptors, including the α6 subunit-containing subtype (α6GABAAR) that is predominantly expressed in cerebellar granule cells and insensitive to diazepam. OBJECTIVES: We explored the action mechanism(s) of hispidulin using hyperdopaminergic mouse models induced by methamphetamine and apomorphine, based on the hyperdopaminergic nature of tic disorders...
September 2016: Psychopharmacology
Jianyu Zhang, Judith P Klinman
Although an enormous and still growing number of biologically diverse methyltransferases have been reported and identified, a comprehensive understanding of the enzymatic methyl transfer mechanism is still lacking. Glycine N-methyltransferase (GNMT), a member of the family that acts on small metabolites as the substrate, catalyzes methyl transfer from S-adenosyl-l-methionine (AdoMet) to glycine to form S-adenosyl-l-homocysteine and sarcosine. We report primary carbon ((12)C/(14)C) and secondary ((1)H3/(3)H3) kinetic isotope effects at the transferred methyl group, together with (1)H3/(3)H3 binding isotope effects for wild-type GNMT and a series of Tyr21 mutants...
July 27, 2016: Journal of the American Chemical Society
Z Pan, Z Fu, Q Song, W Cao, W Cheng, X Xu
Sex hormones play important roles in breast cancer (BC) development. This study investigated associations between BC risk and hormone-related gene variants in Chinese women. In a cohort of 336 patients with histopathologically confirmed BC and 390 age-matched controls, we genotyped seven single nucleotide polymorphisms (SNPs) in five hormone-related genes: estrogen receptor-α (ESR1), aromatase (CYP19), catechol-O-methyl transferase (COMT), sex hormone-binding globulin (SHBG), and glutathione S-transferase (GSTP1)...
2016: Genetics and Molecular Research: GMR
Zheng Dong, Xinyu Sun, Chao Pan, Tianlan Lu, Yonghua Han, Lifang Wang, Hao Yan, Licai Dong, Dai Zhang, Weihua Yue
BACKGROUND: Previous studies suggested that exploratory eye movement (EEM) dysfunction appears to be a biological marker specific to schizophrenia, with an unknown molecular mechanism. Genetic studies indicate that disrupted-in-schizophrenia-1 (DISC1), brain-derived neurotrophic factor (BDNF), and catechol-O-methyl transferase (COMT) genes might be implicated in the etiology of schizophrenia, but not in all populations. OBJECTIVES: The present study aimed to explore associations between these candidate genes and EEM endophenotypes for schizophrenia in a Chinese Han population...
June 9, 2016: Psychiatric Genetics
Juliana Maria de Mello Andrade, Carolina Dos Santos Passos, Maria Angélica Kieling Rubio, Jacqueline Nakau Mendonça, Norberto Peporine Lopes, Amélia Teresinha Henriques
Natural products are important sources of chemical diversity leading to unique scaffolds that can be exploited in the discovery of new drug candidates or chemical probes. In this context, chemical and biological investigation of ferns and lycophytes occurring in Brazil is an approach adopted by our research group aiming at discovering bioactive molecules acting on neurodegeneration targets. In the present study, rosmarinic acid (RA) isolated from Blechnum brasiliense showed an in vitro multifunctional profile characterized by antioxidant effects, and monoamine oxidases (MAO-A and MAO-B) and catechol-O-methyl transferase (COMT) inhibition...
July 25, 2016: Chemico-biological Interactions
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"