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s adenosyl l-methionine

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https://www.readbyqxmd.com/read/29452350/extra-virgin-olive-oil-contains-a-metabolo-epigenetic-inhibitor-of-cancer-stem-cells
#1
Bruna Corominas-Faja, Elisabet Cuyàs, Jesús Lozano-Sánchez, Sílvia Cufí, Sara Verdura, Salvador Fernández-Arroyo, Isabel Borrás-Linares, Begoña Martin-Castillo, Ángel G Martin, Ruth Lupu, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Vicente Micol, Jorge Joven, Antonio Segura-Carretero, Javier A Menendez
Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target sub-populations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24-/low CSC...
February 14, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29449933/a-simplified-characterization-of-s-adenosyl-l-methionine-consuming-enzymes-with-1-step-ez-mtase-a-universal-and-straightforward-coupled-assay-for-in-vitro-and-in-vivo-setting
#2
Emmanuel S Burgos, Ryan O Walters, Derek M Huffman, David Shechter
Methyltransferases use S -adenosyl-l-methionine (SAM) to deposit methyl marks. Many of these epigenetic 'writers' are associated with gene regulation. As cancer etiology is highly correlated with misregulated methylation patterns, methyltransferases are emerging therapeutic targets. Successful assignment of methyltransferases' roles within intricate biological networks relies on (1) the access to enzyme mechanistic insights and (2) the efficient screening of chemical probes against these targets. To characterize methyltransferases in vitro and in vivo , we report a highly-sensitive one-step deaminase-linked continuous assay where the S -adenosyl-l-homocysteine (SAH) enzyme-product is rapidly and quantitatively catabolized to S -inosyl-l-homocysteine (SIH)...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29449868/prediction-of-methionine-and-homocysteine-levels-in-zucker-diabetic-fatty-zdf-rats-as-a-t2dm-animal-model-after-consumption-of-a-methionine-rich-diet
#3
Nayoung Han, Jung-Woo Chae, Jihyun Jeon, Jaeyeon Lee, Hyun-Moon Back, Byungjeong Song, Kwang-Il Kwon, Sang Kyum Kim, Hwi-Yeol Yun
Background: Although alterations in the methionine metabolism cycle (MMC) have been associated with vascular complications of diabetes, there have not been consistent results about the levels of methionine and homocysteine in type 2 diabetes mellitus (T2DM). The aim of the current study was to predict changes in plasma methionine and homocysteine concentrations after simulated consumption of methionine-rich foods, following the development of a mathematical model for MMC in Zucker Diabetic Fatty (ZDF) rats, as a representative T2DM animal model...
2018: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29448137/differential-metabolism-of-l-phenylalanine-in-the-formation-of-aromatic-volatiles-in-melon-cucumis-melo-l-fruit
#4
Itay Gonda, Rachel Davidovich-Rikanati, Einat Bar, Shery Lev, Pliaa Jhirad, Yuval Meshulam, Guy Wissotsky, Vitaly Portnoy, Joseph Burger, Arthur A Schaffer, Yaakov Tadmor, James J Giovannoni, Zhangjun Fei, Aaron Fait, Nurit Katzir, Efraim Lewinsohn
Studies on the active pathways and the genes involved in the biosynthesis of L-phenylalanine-derived volatiles in fleshy fruits are sparse. Melon fruit rinds converted stable-isotope labeled L-phe into more than 20 volatiles. Phenylpropanes, phenylpropenes and benzenoids are apparently produced via the well-known phenylpropanoid pathway involving phenylalanine ammonia lyase (PAL) and being (E)-cinnamic acid a key intermediate. Phenethyl derivatives seemed to be derived from L-phe via a separate biosynthetic route not involving (E)-cinnamic acid and PAL...
February 12, 2018: Phytochemistry
https://www.readbyqxmd.com/read/29427574/new-product-identification-in-the-sterol-metabolism-by-an-industrial-strain-mycobacterium-neoaurum-nrrl-b-3805
#5
Xuemei Li, Xi Chen, Yu Wang, Peiyuan Yao, Rui Zhang, Jinhui Feng, Qiaqing Wu, Dunming Zhu, Yanhe Ma
Mycobacterium neoaurum NRRL B-3805 metabolizes sterols to produce androst-4-en-3,17-dione (AD) as the main product, and androsta-1,4-dien-3,17-dione, 9α-hydroxyandrost-4-en-3,17-dione and 22-hydroxy-23,24-bisnorchol-4-en-3-one have been identified as by-products. In this study, a new by-product was isolated from the metabolites of sterols and identified as methyl 3-oxo-23,24-bisnorchol-4-en-22-oate (BNC methyl ester), which was proposed to be produced via the esterification of BNC catalyzed by an O-methyltransferase using S-adenosyl-l-methionine as the methyl group donor...
February 7, 2018: Steroids
https://www.readbyqxmd.com/read/29425801/analytical-and-clinical-validation-of-an-lc-ms-ms-method-to-measure-thiopurine-s-methyltransferase-activity-by-quantifying-d3-6-mmp
#6
Jing Ma, Christiaan W Sies, Linda S Pike
BACKGROUND: Identification of patients with thiopurine S-methyltransferase (TPMT) deficiency prior to thiopurine drug therapy has become routine clinical practice worldwide. To measure TPMT activity, traditional radiochemical assays have been replaced by chromatographic methods. METHOD: Inspired by the increasing number of isotope labelled sources that may be of benefit for the TPMT assay, a new LC-MS/MS method for TPMT activity was developed and validated. Isotope labelled d3-S-adenosyl-l-methionine (d3-SAM) was selected for the enzymatic methylation of mercaptopurine during sample incubation; d3-6-methylmercaptopurine (d3-6-MMP) with d2-2, 8-hypoxanthine as the internal standard was quantified to ascertain individual TPMT activity...
February 6, 2018: Clinical Biochemistry
https://www.readbyqxmd.com/read/29414770/homocysteine-regulates-fatty-acid-and-lipid-metabolism-in-yeast
#7
Myriam Visram, Maja Radulovic, Sabine Steiner, Nermina Malanovic, Thomas O Eichmann, Heimo Wolinski, Gerald N Rechberger, Oksana Tehlivets
S-adenosyl-L-homocysteine hydrolase (AdoHcy hydrolase; Sah1 in yeast/AHCY in mammals) degrades AdoHcy, a byproduct and strong product inhibitor of S-adenosyl-L-methionine (AdoMet)-dependent methylation reactions, to adenosine and homocysteine (Hcy). This reaction is reversible, so any elevation of Hcy levels, such as in hyperhomocysteinemia (HHcy), drives the formation of AdoHcy, with detrimental consequences for cellular methylation reactions. HHcy, a pathological condition linked to cardiovascular and neurological disorders as well as fatty liver amongst others, is associated with a deregulation of lipid metabolism...
February 6, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29379364/dna-cytosine-5-methyltransferase-3b-dnmt-3b-polymorphism-and-risk-of-down-syndrome-offspring
#8
Cláudia Melo de Moura, Pedro Ribeiro Bastos, Julyana S V Ribeiro, Márcia Gonçalves Ribeiro, Márcia Rodrigues Amorim, Marcelo Aguiar Costa-Lima
Down syndrome (DS) is the most common form of human genetic mental retardation. Several polymorphisms in genes coding folic acid cycle enzymes have been associated to the risk of bearing a DS child; however, the results are controversial. S-adenosyl-l-methionine (SAM) is an important intermediate of folic acid pathway and acts as methyl donor and substrate for DNA (cytosine-5)-methyltransferase 3B (DNMT3B - EC 2.1.1.37) de novo methylation processes during embryogenesis. Recent studies suggest that a functional polymorphism of DNMT 3B in maternal genotype may be associated with a decreased risk of having a DS child...
January 2018: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/29363853/disruption-of-the-methionine-cycle-and-reduced-cellular-gluthathione-levels-underlie-potex-potyvirus-synergism-in-nicotiana-benthamiana
#9
Swarnalok De, Gabriela Chavez-Calvillo, Matti Wahlsten, Kristiina Mäkinen
Infection caused by synergistic interaction of two plant viruses is typically manifested by severe symptoms and increased accumulation of either virus. In potex-potyviral synergism potyviral RNA silencing suppressor HCPro is known to enhance the pathogenicity of the potexvirus counterpart. In line with this Potato virus X (PVX; genus Potexvirus) genomic RNA (gRNA) accumulation and gene expression from subgenomic RNA (sgRNA) increased in Nicotiana benthamiana by Potato virus A (PVA; genus Potyvirus) HCPro expression...
January 24, 2018: Molecular Plant Pathology
https://www.readbyqxmd.com/read/29342140/atomic-structure-of-the-eukaryotic-intramembrane-ras-methyltransferase-icmt
#10
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
#11
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 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29332244/structural-insights-into-the-function-of-elongator
#12
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
#13
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
#14
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
#15
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
#16
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/29226074/characterization-of-auxiliary-iron-sulfur-clusters-in-a-radical-s-adenosylmethionine-enzyme-pqqe-from-methylobacterium-extorquens-am1
#17
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/29206198/genome-wide-comprehensive-analysis-the-molecular-phylogenetic-evaluation-and-tissue-specific-expression-of-sabath-gene-family-in-salvia-miltiorrhiza
#18
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
#19
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
#20
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
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