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s adenosyl l-methionine

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https://www.readbyqxmd.com/read/28726800/role-of-nicotinamide-n-methyltransferase-in-dorsal-striatum-in-cocaine-place-preference
#1
Li Luo, Fei-Fei Shang, Hailei Long, Linhong Jiang, Ruiming Zhu, Qian Zhao, Hui Gu, Jueying Kong, Wei Xu, Yinglan Zhao, Xiaobo Cen
Nicotinamide N-methyltransferase (NNMT) transfers the methyl from S-adenosyl-L-methionine (SAM) to nicotinamide (NA) to produce S-adenosyl-L-homocysteine (SAH) and 1-methylnicotinamide (MeN). NNMT has been implicated in a variety of diseases; however, the role of NNMT in drug addiction is largely unknown. Here, we found that the expression of Nnmt was significantly upregulated in the dorsal striatum (DS) of cocaine-conditioned mice. Cocaine significantly decreased SAM/SAH ratio levels in the DS, which was accompanied with the decreased activities of Rac1 and RhoA...
July 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28720493/crystal-structures-of-monkey-and-mouse-nicotinamide-n-methyltransferase-nnmt-bound-with-end-product-1-methyl-nicotinamide
#2
Srinivasan Swaminathan, Swarnakumari Birudukota, Manish Kumar Thakur, Reejuana Parveen, Saravanan Kandan, Suresh Juluri, Shama Shaik, Niranjan Naranapura Anand, Raghunadha Reddy Burri, Rajendra Kristam, Sridharan Rajagopal, Herman Schreuder, Thomas Langer, Christine Rudolph, Sven Ruf, Saravanakumar Dhakshinamoorthy, Ramachandraiah Gosu, Aimo Kannt
Nicotinamide N-methyltransferase (NNMT) is a S-adenosyl-L-methionine (SAM)-dependent enzyme that catalyzes N-methylation of nicotinamide (NA) and other pyridines to form N-methyl pyridinium ions. Here we report the first ternary complex X-ray crystal structures of monkey NNMT and mouse NNMT in bound form with the primary endogenous product, 1-methyl nicotinamide (MNA) and demethylated cofactor, S-adenosyl-homocysteine (SAH) determined at 2.30 Å and 1.88 Å respectively. The structural fold of these enzymes is identical to human NNMT...
July 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28708454/improving-the-production-of-s-adenosyl-l-methionine-in-escherichia-coli-by-overexpressing-metk
#3
Ping Yu, Pengzhi Zhu
S-adenosyl-L-methionine (SAM) has important applications in many fields including the chemical therapy and the pharmaceutical industry. In this study, the recombinant Escherichia coli strain was constructed for effective production of SAM by introducing the SAM synthase gene (metK). This strain produced 34.5 mg/l of SAM in basic medium in shake flask. Yeast extract, pH and loaded volume had a significant positive effect on the yield of SAM. Their optimal values were 35 g/l, 7.5 and 30 ml, respectively...
July 14, 2017: Preparative Biochemistry & Biotechnology
https://www.readbyqxmd.com/read/28708394/human-viperin-causes-radical-sam-dependent-elongation-of-escherichia-coli-hinting-at-its-physiological-role
#4
Micah T Nelp, Anthony P Young, Branden M Stepanski, Vahe Bandarian
Viperin (virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible) is a widely distributed protein that is expressed in response to infection and causes antiviral effects against a broad spectrum of viruses. Viperin is a member of the radical S-adenosyl-l-methionine (SAM) superfamily of enzymes, which typically employ a 4Fe-4S cluster to reductively cleave SAM to initiate chemistry. Though the specific reaction catalyzed by viperin remains unknown, it has been shown that expression of viperin causes an increase in the fluidity of lipid membranes, which impedes the budding of nascent viral particles from the membrane inhibiting propagation of the infection...
July 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28682528/s-adenosylmethionine-same-for-neuropsychiatric-disorders-a-clinician-oriented-review-of-research
#5
REVIEW
Anup Sharma, Patricia Gerbarg, Teodoro Bottiglieri, Lila Massoumi, Linda L Carpenter, Helen Lavretsky, Philip R Muskin, Richard P Brown, David Mischoulon
OBJECTIVE: A systematic review on S-adenosylmethionine (SAMe) for treatment of neuropsychiatric conditions and comorbid medical conditions. DATA SOURCES: Searches were conducted in PubMed, EMBASE, PsycINFO, Cochrane Library, CINAHL, and Google Scholar databases between July 15, 2015, and September 28, 2016, by combining search terms for SAMe (s-adenosyl methionine or s-adenosyl-l-methionine) with terms for relevant disease states (major depressive disorder, MDD, depression, perinatal depression, human immunodeficiency virus, HIV, Parkinson's, Alzheimer's, dementia, anxiety, schizophrenia, psychotic, 22q11...
June 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28671210/a-mechanistic-study-of-the-non-oxidative-decarboxylation-catalyzed-by-the-radical-s-adenosyl-l-methionine-enzyme-blse-involved-in-blasticidin-s-biosynthesis
#6
Lei Liu, Xinjian Ji, Yongzhen Li, Wenjuan Ji, Tianlu Mo, Wei Ding, Qi Zhang
Decarboxylation is a fundamentally important reaction in biology and involves highly diverse mechanisms. Here we report a mechanistic study of the non-oxidative decarboxylation catalyzed by BlsE, a radical S-adenosyl-l-methionine (SAM) enzyme involved in blasticidin S biosynthesis. Through a series of biochemical analysis with isotopically labeled reagents, we show that the BlsE-catalyzed reaction is initiated by the 5'-deoxyadenosyl (dAdo) radical-mediated hydrogen abstraction from a sugar carbon of the substrate cytosylglucuronic acid (CGA), and does not involve a carboxyl radical as has been proposed for 4-hydroxyphenylacetate decarboxylase (HPAD)...
July 3, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28659447/unravelling-the-relationship-between-the-tsetse-fly-and-its-obligate-symbiont-wigglesworthia-transcriptomic-and-metabolomic-landscapes-reveal-highly-integrated-physiological-networks
#7
XiaoLi Bing, Geoffrey M Attardo, Aurelien Vigneron, Emre Aksoy, Francesca Scolari, Anna Malacrida, Brian L Weiss, Serap Aksoy
Insects with restricted diets rely on obligate microbes to fulfil nutritional requirements essential for biological function. Tsetse flies, vectors of African trypanosome parasites, feed exclusively on vertebrate blood and harbour the obligate endosymbiont Wigglesworthia glossinidia. Without Wigglesworthia, tsetse are unable to reproduce. These symbionts are sheltered within specialized cells (bacteriocytes) that form the midgut-associated bacteriome organ. To decipher the core functions of this symbiosis essential for tsetse's survival, we performed dual-RNA-seq analysis of the bacteriome, coupled with metabolomic analysis of bacteriome and haemolymph collected from normal and symbiont-cured (sterile) females...
June 28, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28656194/excessive-nnos-no-ampk-signaling-activation-mediated-by-the-blockage-of-the-cbs-h2s-system-contributes-to-oxygen%C3%A2-glucose-deprivation%C3%A2-induced-endoplasmic-reticulum-stress-in-pc12%C3%A2-cells
#8
Rui Zhang, Yong-Quan Lin, Wei-Sheng Wang, Xin-Qiang Wang
Hypoxic‑ischemia stress causes severe brain injury, leading to death and disability worldwide. Although it has been reported that endoplasmic reticulum (ER) stress is an essential step in the progression of hypoxia or ischemia‑induced brain injury, the underlying molecular mechanisms are and have not yet been fully elucidated. Accumulating evidence has indicated that both nitric oxide (NO) and hydrogen sulfide (H2S) play an important role in the development of cerebral ischemic injury. In the present study, we aimed to investigate the effect of the association between NO signaling and the cystathionine β‑synthase (CBS)/H2S system on ER stress in a cell model of cerebral hypoxia‑ischemia injury...
June 21, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28644475/post-translational-modification-of-ribosomally-synthesized-peptides-by-a-radical-sam-epimerase-in-bacillus-subtilis
#9
Alhosna Benjdia, Alain Guillot, Pauline Ruffié, Jérôme Leprince, Olivier Berteau
Ribosomally synthesized peptides are built out of L-amino acids, whereas D-amino acids are generally the hallmark of non-ribosomal synthetic processes. Here we show that the model bacterium Bacillus subtilis is able to produce a novel type of ribosomally synthesized and post-translationally modified peptide that contains D-amino acids, and which we propose to call epipeptides. We demonstrate that a two [4Fe-4S]-cluster radical S-adenosyl-L-methionine (SAM) enzyme converts L-amino acids into their D-counterparts by catalysing Cα-hydrogen-atom abstraction and using a critical cysteine residue as the hydrogen-atom donor...
July 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28623948/one-carbon-metabolism-cognitive-impairment-and-csf-measures-of-alzheimer-pathology-homocysteine-and-beyond
#10
Loïc Dayon, Seu Ping Guiraud, John Corthésy, Laeticia Da Silva, Eugenia Migliavacca, Domilė Tautvydaitė, Aikaterini Oikonomidi, Barbara Moullet, Hugues Henry, Sylviane Métairon, Julien Marquis, Patrick Descombes, Sebastiano Collino, François-Pierre J Martin, Ivan Montoliu, Martin Kussmann, Jérôme Wojcik, Gene L Bowman, Julius Popp
BACKGROUND: Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults...
June 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28553945/targeting-s-adenosylmethionine-biosynthesis-with-a-novel-allosteric-inhibitor-of-mat2a
#11
Casey L Quinlan, Stephen E Kaiser, Ben Bolaños, Dawn Nowlin, Rita Grantner, Shannon Karlicek-Bryant, Jun Li Feng, Stephen Jenkinson, Kevin Freeman-Cook, Stephen G Dann, Xiaoli Wang, Peter A Wells, Valeria R Fantin, Al E Stewart, Stephan K Grant
S-Adenosyl-L-methionine (SAM) is an enzyme cofactor used in methyl transfer reactions and polyamine biosynthesis. The biosynthesis of SAM from ATP and L-methionine is performed by the methionine adenosyltransferase enzyme family (Mat; EC 2.5.1.6). Human methionine adenosyltransferase 2A (Mat2A), the extrahepatic isoform, is often deregulated in cancer. We identified a Mat2A inhibitor, PF-9366, that binds an allosteric site on Mat2A that overlaps with the binding site for the Mat2A regulator, Mat2B. Studies exploiting PF-9366 suggested a general mode of Mat2A allosteric regulation...
July 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28546903/comprehensive-reconstruction-and-evaluation-of-pichia-pastoris-genome-scale-metabolic-model-that-accounts-for-1243-orfs
#12
Rui Ye, Mingzhi Huang, Hongzhong Lu, Jiangchao Qian, Weilu Lin, Ju Chu, Yingping Zhuang, Siliang Zhang
BACKGROUND: Pichia pastoris is one of the most important cell factories for production of industrial enzymes and heterogenous proteins. The genome-scale metabolic model of high quality is crucial for comprehensive understanding of the P. pastoris metabolism. METHODS: In this paper, we upgraded P. pastoris genome-scale metabolic model based on the combination of latest genome annotations and literatures. Then the performance of the new model was evaluated using the Cobra Toolbox v2...
2017: Bioresources and Bioprocessing
https://www.readbyqxmd.com/read/28518408/s-adenosylmethionine-mediated-apoptosis-is-potentiated-by-autophagy-inhibition-induced-by-chloroquine-in-human-breast-cancer-cells
#13
Donatella Delle Cave, Vincenzo Desiderio, Laura Mosca, Concetta P Ilisso, Luigi Mele, Michele Caraglia, Giovanna Cacciapuoti, Marina Porcelli
The naturally occurring sulfonium compound S-adenosyl-L-methionine (AdoMet) is an ubiquitous sulfur-nucleoside that represents the main methyl donor in numerous methylation reactions. In recent years, it has been shown that AdoMet possesses antiproliferative properties in various cancer cells, but the molecular mechanisms at the basis of the effect induced by AdoMet have been only in part investigated. In the present study, we found that AdoMet strongly inhibited the proliferation of breast cancer cells MCF-7 by inducing both autophagy and apoptosis...
May 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28489377/svetamycins-a-g-unusual-piperazic-acid-containing-peptides-from-streptomyces-sp
#14
Denis Dardić, Gianluigi Lauro, Giuseppe Bifulco, Patricia Laboudie, Peyman Sakhaii, Armin Bauer, Andreas Vilcinskas, Peter E Hammann, Alberto Plaza
Seven new halogenated peptides termed svetamycins A-G (1-7) have been isolated from laboratory cultures of a Streptomyces sp. Svetamycins A-D, F, and G are cyclic depsipeptides, whereas svetamycin E is a linear analogue of svetamycin C. Their structures were determined using extensive spectroscopic analysis, and their stereochemical configuration was established by a combination of NMR data, quantum mechanical calculations, and chemical derivatizations. Svetamycins are characterized by the presence of a hydroxyl acetic acid and five amino acids including a rare 4,5-dihydroxy-2,3,4,5-tetrahydropyridazine-3-carboxylic acid, a γ-halogenated piperazic acid, and a novel δ-methylated piperazic acid in svetamycins B-C, E, and G...
June 6, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28484204/hydrogen-sulfide-improves-cardiomyocyte-function-in-a-cardiac-arrest-model
#15
Nahuel Aquiles Garcia, Javier Moncayo-Arlandi, Alejandro Vazquez, Patricia Genovés, Conrado J Calvo, José Millet, Nuria Martí, Carmen Aguado, Erwin Knecht, Iñigo Valiente-Alandi, José A Montero, Antonio Díez-Juan, Pilar Sepúlveda
BACKGROUND Cardioplegic arrest is a common procedure for many types of cardiac surgery, and different formulations have been proposed to enhance its cardio-protective effect. Hydrogen sulfide is an important signaling molecule that has cardio-protective properties. We therefore studied the cardio-protective effect of hydrogen sulfide in cardiac cell culture and its potential therapeutic use in combination with cardioplegia formulations. MATERIAL AND METHODS We added hydrogen sulfide donor GYY4137 to HL-1 cells to study its protective effect in nutrient starved conditions...
May 9, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28469408/modification-of-s-adenosyl-l-homocysteine-as-inhibitor-of-nonstructural-protein-5-methyltransferase-dengue-virus-through-molecular-docking-and-molecular-dynamics-simulation
#16
Usman Sumo Friend Tambunan, Mochammad Arfin Fardiansyah Nasution, Fauziah Azhima, Arli Aditya Parikesit, Erwin Prasetya Toepak, Syarifuddin Idrus, Djati Kerami
Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world's population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S-adenosyl-l-methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2'OH, resulting in S-adenosyl-l-homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test...
2017: Drug Target Insights
https://www.readbyqxmd.com/read/28463515/rational-design-of-bisubstrate-type-analogues-as-inhibitors-of-dna-methyltransferases-in-cancer-cells
#17
Ludovic Halby, Yoann Menon, Elodie Rilova, Dany Pechalrieu, Véronique Masson, Celine Faux, Mohamed Amine Bouhlel, Marie-Hélène David-Cordonnier, Natacha Novosad, Yannick Aussagues, Arnaud Samson, Laurent Lacroix, Fréderic Ausseil, Laurence Fleury, Dominique Guianvarc'h, Clotilde Ferroud, Paola B Arimondo
Aberrant DNA hypermethylation of promoter of tumor suppressor genes is commonly observed in cancer, and its inhibition by small molecules is promising for their reactivation. Here we designed bisubstrate analogues-based inhibitors, by mimicking each substrate, the S-adenosyl-l-methionine and the deoxycytidine, and linking them together. This approach resulted in quinazoline-quinoline derivatives as potent inhibitors of DNMT3A and DNMT1, some showing certain isoform selectivity. We highlighted the importance of (i) the nature and rigidity of the linker between the two moieties for inhibition, as (ii) the presence of the nitrogen on the quinoline group, and (iii) of a hydrophobic group on the quinazoline...
June 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28461153/a-coupled-photometric-assay-for-characterization-of-s-adenosyl-l-homocysteine-hydrolases-in-the-physiological-hydrolytic-direction
#18
Lyn L Kailing, Daniela Bertinetti, Friedrich W Herberg, Ioannis V Pavlidis
S-Adenosyl-L-homocysteine hydrolases (SAHases) are important metabolic enzymes and their dysregulation is associated with some severe diseases. In vivo they catalyze the hydrolysis of S-adenosyl-L-homocysteine (SAH), the by-product of methylation reactions in various organisms. SAH is a potent inhibitor of methyltransferases, thus its removal from the equilibrium is an important requirement for methylation reactions. SAH hydrolysis is also the first step in the cellular regeneration process of the methyl donor S-adenosyl-L-methionine (SAM)...
April 28, 2017: New Biotechnology
https://www.readbyqxmd.com/read/28448141/correction-to-design-of-potent-and-druglike-nonphenolic-inhibitors-for-catechol-o-methyltransferase-derived-from-a-fragment-screening-approach-targeting-the-s-adenosyl-l-methionine-pocket
#19
Christian Lerner, Roland Jakob-Roetne, Bernd Buettelmann, Andreas Ehler, Markus G Rudolph, Rosa María Rodríguez Sarmiento
No abstract text is available yet for this article.
May 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28435838/thiol-trapping-and-metabolic-redistribution-of-sulfur-metabolites-enable-cells-to-overcome-cysteine-overload
#20
Anup Arunrao Deshpande, Muskan Bhatia, Sunil Laxman, Anand Kumar Bachhawat
Cysteine is an essential requirement in living organisms. However, due to its reactive thiol side chain, elevated levels of intracellular cysteine can be toxic and therefore need to be rapidly eliminated from the cellular milieu. In mammals and many other organisms, excess cysteine is believed to be primarily eliminated by the cysteine dioxygenase dependent oxidative degradation of cysteine, followed by the removal of the oxidative products. However, other mechanisms of tackling excess cysteine are also likely to exist, but have not thus far been explored...
March 27, 2017: Microbial Cell
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