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S-Adenosyl methionine

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https://www.readbyqxmd.com/read/28623948/one-carbon-metabolism-cognitive-impairment-and-csf-measures-of-alzheimer-pathology-homocysteine-and-beyond
#1
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/28615450/cellular-requirements-for-iron-sulfur-cluster-insertion-into-the-antiviral-radical-sam-protein-viperin
#2
Arunkumar S Upadhyay, Oliver Stehling, Christakis Panayiotou, Ralf Rösser, Roland Lill, Anna K Överby
Viperin (RSAD2) is an interferon-stimulated antiviral protein that belongs to the radical S-adenosyl methionine (SAM) enzyme family. Viperin's iron-sulfur (Fe/S) cluster is critical for its antiviral activity against many different viruses. CIA1 (CIAO1), an essential component of the cytosolic iron-sulfur protein assembly (CIA) machinery, is crucial for Fe/S cluster insertion into viperin and hence for viperin's antiviral activity. In the CIA pathway, CIA1 cooperates with CIA2A, CIA2B, and MMS19 targeting factors to form various complexes that mediate the dedicated maturation of specific Fe/S recipient proteins...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28601431/serine-and-functional-metabolites-in-cancer
#3
REVIEW
Alice C Newman, Oliver D K Maddocks
Folate metabolism functions to supply one-carbon units that are vital for a range of biochemical reactions. Cancer cells can utilise serine as a major source of one-carbon units, rendering them dependent upon extracellular serine uptake or de novo serine synthesis for maximal growth and proliferation. One-carbon units are required for the production of critical cellular components, such as nucleotides, which enable cancer cells to maintain high proliferate rates. Of recent interest, one-carbon metabolism contributes to the biosynthesis and recycling of functional metabolites, such as ATP, S-adenosyl-methionine (SAM), and NAD(P)H, with important downstream consequences for cancer cell survival...
June 7, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28601227/trmd-a-methyl-transferase-for-trna-methylation-with-m-1-g37
#4
Ya-Ming Hou, Ryuma Matsubara, Ryuichi Takase, Isao Masuda, Joanna I Sulkowska
TrmD is an S-adenosyl methionine (AdoMet)-dependent methyl transferase that synthesizes the methylated m(1)G37 in tRNA. TrmD is specific to and essential for bacterial growth, and it is fundamentally distinct from its eukaryotic and archaeal counterpart Trm5. TrmD is unusual by using a topological protein knot to bind AdoMet. Despite its restricted mobility, the TrmD knot has complex dynamics necessary to transmit the signal of AdoMet binding to promote tRNA binding and methyl transfer. Mutations in the TrmD knot block this intramolecular signaling and decrease the synthesis of m(1)G37-tRNA, prompting ribosomes to +1-frameshifts and premature termination of protein synthesis...
2017: Enzymes
https://www.readbyqxmd.com/read/28576826/archaeal-fibrillarin-nop5-heterodimer-2-o-methylates-rna-independently-of-the-c-d-guide-rnp-particle
#5
Miglė Tomkuvienė, Janina Ličytė, Ingrida Olendraitė, Zita Liutkevičiūtė, Béatrice Clouet-d'Orval, Saulius Klimašauskas
Archaeal fibrillarin (aFib) is a well-characterized S-Adenosyl methionine (SAM)-dependent RNA 2'-O-methyltransferase that is known to act in a large C/D ribonucleoprotein (RNP) complex together with Nop5 and L7Ae proteins and a box C/D guide RNA. In the reaction, the guide RNA is critical to direct the methylation reaction to a specific site in tRNA or rRNA by sequence complementarity. Here we show that Pyrococcus abyssi aFib-Nop5 heterodimer can alone perform a SAM-dependent 2'-O-methylation of 16S and 23S ribosomal RNAs in vitro independently of L7Ae and C/D guide RNAs...
June 2, 2017: RNA
https://www.readbyqxmd.com/read/28556625/suppression-of-a-methionine-synthase-by-calmodulin-under-environmental-stress-in-the-entomopathogenic-fungus-beauveria-bassiana
#6
Jiyoung Kim, Junsang Oh, Deok-Hyo Yoon, Gi-Ho Sung
Methionine synthase (MetE, EC 2.1.1.14) catalyzes the final step in the methionine biosynthetic pathway. Methionine biosynthesis plays a major role in protein biogenesis and is the source of S-adenosyl methionine (SAM), the universal donor of methyl groups. In this study, we demonstrated that BbMetE acts as a typical MetE enzyme in the entomopathogenic fungus Beauveria bassiana. In addition, we found that BbMetE binds to calmodulin (CaM) in vitro and in vivo. The functional role of CaM binding to BbMetE was to negatively regulate BbMetE activity in B...
May 29, 2017: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/28553945/targeting-s-adenosylmethionine-biosynthesis-with-a-novel-allosteric-inhibitor-of-mat2a
#7
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/28552342/interplay-between-mitochondrial-metabolism-and-oxidative-stress-in-ischemic-stroke-an-epigenetic-connection
#8
REVIEW
Parimala Narne, Vimal Pandey, Prakash Babu Phanithi
The advent of epigenetics brought in a tectonic shift in the understanding of molecular basis of complex diseases like ischemic stroke (IS). Substantial scientific inquiry into the epigenetic basis of neurodegenerative diseases has bolstered the idea that altered carbon flux into central carbon metabolism and disturbed redox states govern the attendant transcriptional profiles through stochastic epigenetic changes. In view of an increasing understanding of the link between mitochondrial energy metabolism, oxidative stress and epigenetics in IS, the hitherto underappreciated 'neuroenergetics' is gaining sustained attention...
May 24, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28546903/comprehensive-reconstruction-and-evaluation-of-pichia-pastoris-genome-scale-metabolic-model-that-accounts-for-1243-orfs
#9
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/28535932/charting-novel-allergens-from-date-palm-pollen-phoenix-sylvestris-using-homology-driven-proteomics
#10
Bodhisattwa Saha, Naren Pandey, Swati Gupta Bhattacharya
Pollen grains from Phoenix sylvestris (date palm), a commonly cultivated tree in India has been found to cause severe allergic diseases in an increasing percentage of hypersensitive individuals. To unearth its allergenic components, pollen protein were profiled by two-dimensional gel electrophoresis followed by immunoblotting with date palm pollen sensitive patient sera. Allergens were identified by MALDI-TOF/TOF employing a layered proteomic approach combining conventional database dependent search and manual de novo sequencing followed by homology-based search as Phoenix sylvestris is unsequenced...
May 20, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28518408/s-adenosylmethionine-mediated-apoptosis-is-potentiated-by-autophagy-inhibition-induced-by-chloroquine-in-human-breast-cancer-cells
#11
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/28515364/nicotinamide-metabolism-regulates-glioblastoma-stem-cell-maintenance
#12
Jinkyu Jung, Leo J Y Kim, Xiuxing Wang, Qiulian Wu, Tanwarat Sanvoranart, Christopher G Hubert, Briana C Prager, Lisa C Wallace, Xun Jin, Stephen C Mack, Jeremy N Rich
Metabolic dysregulation promotes cancer growth through not only energy production, but also epigenetic reprogramming. Here, we report that a critical node in methyl donor metabolism, nicotinamide N-methyltransferase (NNMT), ranked among the most consistently overexpressed metabolism genes in glioblastoma relative to normal brain. NNMT was preferentially expressed by mesenchymal glioblastoma stem cells (GSCs). NNMT depletes S-adenosyl methionine (SAM), a methyl donor generated from methionine. GSCs contained lower levels of methionine, SAM, and nicotinamide, but they contained higher levels of oxidized nicotinamide adenine dinucleotide (NAD+) than differentiated tumor cells...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28489377/svetamycins-a-g-unusual-piperazic-acid-containing-peptides-from-streptomyces-sp
#13
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
#14
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
#15
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
#16
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...
May 23, 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
#17
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
#18
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
#19
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
https://www.readbyqxmd.com/read/28430424/elucidation-of-the-stereospecificity-of-c-methyltransferases-from-trans-at-polyketide-synthases
#20
Xinqiang Xie, Chaitan Khosla, David E Cane
S-Adenosyl methionine (SAM)-dependent C-methyltransferases are responsible for the C2-methylation of 3-ketoacyl-acyl carrier protein (ACP) intermediates to give the corresponding 2-methy-3-ketoacyl-ACP products during bacterial polyketide biosynthesis mediated by trans-AT polyketide synthases that lack integrated acyl transferase (AT) domains. A coupled ketoreductase (KR) assay was used to assign the stereochemistry of the C-methyltransferase-catalyzed reaction. Samples of chemoenzymatically generated 3-ketopentanoyl-ACP (9) were incubated with SAM and BonMT2 from module 2 of the bongkrekic acid polyketide synthase...
May 3, 2017: Journal of the American Chemical Society
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