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S-Adenosyl methionine

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https://www.readbyqxmd.com/read/29343446/s-adenosyl-methionine-prevents-asd-like-behaviors-triggered-by-early-postnatal-valproic-acid-exposure-in-very-young-mice
#1
Asher Ornoy, Liza Weinstein-Fudim, Matanel Tfilin, Zivanit Ergaz, Joseph Yanai, Moshe Szyf, Gadi Turgeman
INTRODUCTION: A common animal model of ASD is the one induced by valproic acid (VPA), inducing epigenetic changes and oxidative stress. We studied the possible preventive effect of the methyl donor for epigenetic enzymatic reactions, S-adenosine methionine (SAM), on ASD like behavioral changes and on redox potential in the brain and liver in this model. METHODS: ICR albino mice were injected on postnatal day 4 with one dose of 300 mg/kg of VPA, with normal saline (controls) or with VPA and SAM that was given orally for 3 days at the dose of 30 mg/kg body weight...
January 14, 2018: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/29342140/atomic-structure-of-the-eukaryotic-intramembrane-ras-methyltransferase-icmt
#2
Melinda M Diver, Leanne Pedi, Akiko Koide, Shohei Koide, Stephen B Long
The maturation of RAS GTPases and approximately 200 other cellular CAAX proteins involves three enzymatic steps: addition of a farnesyl or geranylgeranyl prenyl lipid to the cysteine (C) in the C-terminal CAAX motif, proteolytic cleavage of the AAX residues and methylation of the exposed prenylcysteine residue at its terminal carboxylate. This final step is catalysed by isoprenylcysteine carboxyl methyltransferase (ICMT), a eukaryote-specific integral membrane enzyme that resides in the endoplasmic reticulum...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29340929/s-adenosyl-methionine-and-transmethylation-pathways-in-neuropsychiatric-diseases-throughout-life
#3
Jin Gao, Catherine M Cahill, Xudong Huang, Joshua L Roffman, Stefania Lamon-Fava, Maurizio Fava, David Mischoulon, Jack T Rogers
S-Adenosyl methionine (SAMe), as a major methyl donor, exerts its influence on central nervous system function through cellular transmethylation pathways, including the methylation of DNA, histones, protein phosphatase 2A, and several catecholamine moieties. Based on available evidence, this review focuses on the lifelong range of severe neuropsychiatric and neurodegenerative diseases and their associated neuropathologies, which have been linked to the deficiency/load of SAMe production or/and the disturbance in transmethylation pathways...
January 16, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29340097/s-adenosyl-methionine-sam-alters-the-transcriptome-and-methylome-and-specifically-blocks-growth-and-invasiveness-of-liver-cancer-cells
#4
Yan Wang, ZhongSheng Sun, Moshe Szyf
S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to have chemo- protective activity against liver cancer, however the molecular footprint of SAM is unknown. We show here that SAM selectively inhibits growth, transformation and invasiveness of hepatocellular carcinoma cell lines but not normal primary liver cells. Analysis of the transcriptome of SAM treated and untreated liver cancer cell lines HepG2 and SKhep1 and primary liver cells reveals pathways involved in cancer and metastasis that are upregulated in cancer cells and are downregulated by SAM...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29332244/structural-insights-into-the-function-of-elongator
#5
REVIEW
Udit Dalwadi, Calvin K Yip
Conserved from yeast to humans, Elongator is a protein complex implicated in multiple processes including transcription regulation, α-tubulin acetylation, and tRNA modification, and its defects have been shown to cause human diseases such as familial dysautonomia. Elongator consists of two copies of six core subunits (Elp1, Elp2, Elp3, Elp4, Elp5, and Elp6) that are organized into two subcomplexes: Elp1/2/3 and Elp4/5/6 and form a stable assembly of ~ 850 kDa in size. Although the catalytic subunit of Elongator is Elp3, which contains a radical S-adenosyl-L-methionine (SAM) domain and a putative histone acetyltransferase domain, the Elp4/5/6 subcomplex also possesses ATP-modulated tRNA binding activity...
January 13, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29320176/discovery-of-bisubstrate-inhibitors-of-nicotinamide-n-methyltransferase-nnmt
#6
Nicolas Babault, Abdellah Allali-Hassani, Fengling Li, Jie Fan, Alex Yue, Kevin Ju, Feng Liu, Masoud Vedadi, Jing Liu, Jian Jin
Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of pyridine-containing compounds using the cofactor S-5'-adenosyl-L-methionine (SAM) as the methyl group donor. Through the regulation of the levels of its substrates, cofactor, and products, NNMT plays important role in physiology and pathophysiology. Overexpression of NNMT has been implicated in various human diseases. Potent and selective small-molecule NNMT inhibitors are valuable chemical tools for testing biological and therapeutic hypotheses...
January 10, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29306799/purine-salvage-in-plants
#7
REVIEW
Hiroshi Ashihara, Claudio Stasolla, Tatsuhito Fujimura, Alan Crozier
Purine bases and nucleosides are produced by turnover of nucleotides and nucleic acids as well as from some cellular metabolic pathways. Adenosine released from the S-adenosyl-L-methionine cycle is linked to many methyltransferase reactions, such as the biosynthesis of caffeine and glycine betaine. Adenine is produced by the methionine cycles, which is related to other biosynthesis pathways, such those for the production of ethylene, nicotianamine and polyamines. These purine compounds are recycled for nucleotide biosynthesis by so-called "salvage pathways"...
January 4, 2018: Phytochemistry
https://www.readbyqxmd.com/read/29300094/1-2-diol-dehydration-by-the-radical-sam-enzyme-aprd4-a-matter-of-proton-circulation-and-substrate-flexibility
#8
Wan-Qiu Liu, Patricia Amara, Jean-Marie Mouesca, Xinjian Ji, Oriane Renoux, Lydie Martin, Chen Zhang, Qi Zhang, Yvain Nicolet
Regiospecific dehydration of vicinal diols by enzymes is a difficult reaction that usually requires activation by dedicated organic cofactors. The enzymatic use of radical-based chemistry is an effective but challenging alternative as radical intermediates are difficult to control. Here we report the X-ray structure of the radical S-adenosyl-L-methionine (SAM) dehydratase AprD4 involved in the biosynthesis of the aminoglycoside (AG) antibiotic apramycin. Using in vitro characterizations and theoretical calculations based on our crystal structure, we have been able to propose a detailed mechanism of AprD4 catalysis, which involves a complex partially substrate-induced proton relay network in the enzyme active site and highlights the key role of the protein matrix in driving high-energy intermediates...
January 4, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29277012/photoelectrochemical-biosensor-for-hen1-rna-methyltransferase-detection-using-peroxidase-mimics-ptcu-nfs-and-poly-u-polymerase-mediated-rna-extension
#9
Haiyan Wang, Libang Zhu, Junling Duan, Minghui Wang, Huanshun Yin, Po Wang, Shiyun Ai
2'-O-methyl group on the 3' terminal nucleotide in plant microRNAs, as one kind of RNA methylations, is caused by HEN1 RNA methyltransferase (HENMT1), which is thought to be crucial for ribosome biogenesis and function. Herein, a simple and label-free PEC biosensing method was proposed for assay of HENMT1 activity and inhibitor screening based on peroxidase mimic PtCu nanoframes (PtCu NFs) catalytic signal amplification. In this work, MoS2@Graphene quantum dots/Phosphorus-doped rodlike carbon nitride (MoS2@GQDs/P-RCN) heterojunction was used as photoactive materials...
December 21, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29241413/novel-missense-mutations-in-gidb-gene-associated-with-streptomycin-resistance-in-mycobacterium-tuberculosis-insights-from-molecular-dynamics
#10
Bharati Pandey, Sonam Grover, Sukriti Goyal, Salma Jamal, Aditi Singh, Jagdeep Kaur, Abhinav Grover
Streptomycin was the first antibiotic used for the treatment of tuberculosis by inhibiting translational proof reading. Point mutation in gidB gene encoding S-adenosyl methionine (SAM)-dependent 7-methylguanosine (m7G) methyltransferase required for methylation of 16S rRNA confers streptomycin (STR) resistance. As there was no structural substantiation experimentally, gidB protein model was built by threading algorithm. In this work, molecular dynamics (MD) simulations coupled with binding free energy calculations were performed to outline the mechanism underlying high-level streptomycin resistance associated with three novel missense mutants including S70R, T146M and R187M...
December 14, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29232372/attenuated-expression-of-mtr-in-both-prenatally-androgenized-mice-and-women-with-the-hyperandrogenic-phenotype-of-pcos
#11
Lei Lei, Lijun Ding, Jing Su, Mengyuan Liu, Qingqing Shi, Jianjun Zhou, Haixiang Sun, Guijun Yan
Polycystic ovary syndrome (PCOS) is a common endocrine, metabolic and heterogeneous disorder in women of reproductive age, the exact etiology of which remains unknown. To unravel the molecular mechanisms underlying the hyperandrogenic phenotype of PCOS, prenatally androgenized (PNA) mice were used to mimic this phenotype in women with PCOS. Using microarray analysis, 1188 differentially expressed genes, including 671 upregulated and 517 downregulated genes, were identified in ovaries from PNA mice. Five differentially expressed genes (Aldh1a7, Bhmt, Mtr, Nrcam, Ptprg) were validated, and decreased MTR expression was shown in ovaries of PNA mice...
2017: PloS One
https://www.readbyqxmd.com/read/29226074/characterization-of-auxiliary-iron-sulfur-clusters-in-a-radical-s-adenosylmethionine-enzyme-pqqe-from-methylobacterium-extorquens-am1
#12
Natsaran Saichana, Katsuyuki Tanizawa, Hiroshi Ueno, Jiří Pechoušek, Petr Novák, Jitka Frébortová
PqqE is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the initial reaction of pyrroloquinoline quinone (PQQ) biosynthesis. PqqE belongs to the SPASM (subtilosin/PQQ/anaerobic sulfatase/mycofactocin maturating enzymes) subfamily of the radical SAM superfamily and contains multiple Fe-S clusters. To characterize the Fe-S clusters in PqqE from Methylobacterium extorquens AM1, Cys residues conserved in the N-terminal signature motif (CX 3 CX 2C) and the C-terminal seven-cysteine motif (CX 9-15 GX 4 CX n CX 2 CX 5 CX 3 CX n C; n = an unspecified number) were individually or simultaneously mutated into Ser...
December 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29212039/comprehensive-mapping-of-pluripotent-stem-cell-metabolism-using-dynamic-genome-scale-network-modeling
#13
Sriram Chandrasekaran, Jin Zhang, Zhen Sun, Li Zhang, Christian A Ross, Yu-Chung Huang, John M Asara, Hu Li, George Q Daley, James J Collins
Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by the lack of genome-scale network models. Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells. Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29206198/genome-wide-comprehensive-analysis-the-molecular-phylogenetic-evaluation-and-tissue-specific-expression-of-sabath-gene-family-in-salvia-miltiorrhiza
#14
Bin Wang, Shiqiang Wang, Zhezhi Wang
The plant SABATH gene family is a group of O-methyltransferases (O-MTs), which belongs to the S-adenosyl-l-methionine-dependent methyltransferases (SAM-MTs). The resulting reaction products of SABATH genes play an important role in various processes of plant development. In this study, a total of 30 SABATH genes were detected in Salvia miltiorrhiza, which is an important medicinal plant, widely used to treat cardiovascular disease. Multiple sequence alignment and phylogenetic analyses showed that SmSABATH genes could be classified into three groups...
December 5, 2017: Genes
https://www.readbyqxmd.com/read/29204715/insight-into-the-reaction-mechanism-of-lipoyl-synthase-a-qm-mm-study
#15
Geng Dong, Lili Cao, Ulf Ryde
Lipoyl synthase (LipA) catalyses the final step of the biosynthesis of the lipoyl cofactor by insertion of two sulfur atoms at the C6 and C8 atoms of the protein-bound octanoyl substrate. In this reaction, two [4Fe4S] clusters and two molecules of S-adenosyl-L-methionine are used. One of the two FeS clusters is responsible for the generation of a powerful oxidant, the 5'-deoxyadenosyl radical (5'-dA•). The other (the auxiliary cluster) is the source of both sulfur atoms that are inserted into the substrate...
December 4, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29199993/crystal-structure-of-sam-dependent-methyltransferase-from-pyrococcus-horikoshii
#16
K J Pampa, S Madan Kumar, M K Hema, Karthik Kumara, S Naveen, Naoki Kunishima, N K Lokanath
Methyltransferases (MTs) are enzymes involved in methylation that are needed to perform cellular processes such as biosynthesis, metabolism, gene expression, protein trafficking and signal transduction. The cofactor S-adenosyl-L-methionine (SAM) is used for catalysis by SAM-dependent methyltransferases (SAM-MTs). The crystal structure of Pyrococcus horikoshii SAM-MT was determined to a resolution of 2.1 Å using X-ray diffraction. The monomeric structure consists of a Rossmann-like fold (domain I) and a substrate-binding domain (domain II)...
December 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/29194039/validation-of-a-high-performance-liquid-chromatography-method-for-thiopurine-s-methyltransferase-activity-in-whole-blood-using-6-mercaptopurine-as-substrate
#17
Hannah Rieger, Patrik Schmidt, Elke Schaeffeler, Manabu Abe, Mira Schiffhauer, Matthias Schwab, Nicolas von Ahsen, Gabriela Zurek, Hartmut Kirchherr, Maria Shipkova, Eberhard Wieland
BACKGROUND: Variation in metabolism, toxicity and therapeutic efficacy of thiopurine drugs is largely influenced by genetic polymorphisms in the thiopurine S-methyltransferase (TPMT) gene. Determination of TPMT activity is routinely performed in patients to adjust drug therapy. METHODS: We further optimized a previously established high-performance liquid chromatography (HPLC) method by measuring TPMT activity in whole blood instead of isolated erythrocytes, which is based on conversion of 6-mercaptopurine to 6-methylmercaptopurine using S-adenosyl-methionine as methyl donor...
December 1, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29184954/reversible-modification-of-dna-by-methyltransferase-catalyzed-transfer-and-light-triggered-removal-of-photo-caging-groups
#18
Lea Anhäuser, Fabian Muttach, Andrea Rentmeister
Methyltransferases are powerful tools for site-specific transfer of non-natural functional groups from synthetic analogs of their cosubstrate S-adenosyl-l-methionine (AdoMet). We present a new class of AdoMet analogs containing photo-caging (PC) groups in their side chain, enzymatic transfer of PC groups by a promiscuous DNA MTase as well as light-triggered removal from the target DNA. This strategy provides a new avenue to reversibly modulate the functionality of DNA at MTase target sites.
November 29, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29180119/cyclopropane-fatty-acid-synthesis-affects-cell-shape-and-acid-resistance-in-leishmania-mexicana
#19
Wei Xu, Sumit Mukherjee, Yu Ning, Fong-Fu Hsu, Kai Zhang
Cyclopropane fatty acid synthase (CFAS) catalyzes the transfer of a methylene group from S-adenosyl methionine to an unsaturated fatty acid, generating a cyclopropane fatty acid (CFA). The gene encoding CFAS is present in many bacteria and several Leishmania spp. including Leishmania mexicana, Leishmania infantum and Leishmania braziliensis. In this study, we characterized the CFAS-null and -overexpression mutants in L. mexicana, the causative agent for cutaneous leishmaniasis in Mexico and central America...
November 24, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/29176927/conceptualizing-eukaryotic-metabolic-sensing-and-signaling
#20
Sunil Laxman
For almost all cells, nutrient availability, from glucose to amino acids, dictates their growth or developmental programs. This nutrient availability is closely coupled to the overall intracellular metabolic state of the cell. Therefore, cells have evolved diverse, robust and versatile modules to sense intracellular metabolic states, activate signaling outputs and regulate outcomes to these states. Yet, signaling and metabolism have been viewed as important but separate. This short review attempts to position aspects of intracellular signaling from a metabolic perspective, highlighting how conserved, core principles of metabolic sensing and signaling can emerge from an understanding of metabolic regulation...
March 2017: Journal of the Indian Institute of Science
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