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S-Adenosyl methionine

Kilmer S McCully
The indoleamine hormone melatonin is synthesized by the pineal gland, controls circadian rhythm, and is dependent upon adenosyl methionine for enzymatic synthesis of melatonin from N-acetyl serotonin. Pineal melatonin secretion declines dramatically with aging and dementia. Elevated plasma homocysteine is a risk factor for atherosclerosis and Alzheimer's disease, and the marked decline in adenosyl methionine with aging leads to dysregulation of methionine metabolism and hyperhomocysteinemia. Thioretinaco ozonide is a disulfonium complex formed from thioretinamide, cobalamin, and ozone, which binds the alpha and gamma-phosphate groups of adenosine triphosphate (ATP) and oxygen in the process of oxidative phosphorylation within mitochondria...
January 2018: Annals of Clinical and Laboratory Science
Jiaxuan Guo, Shufang Wang, XiaoYang Yu, Rui Dong, Yuzhong Li, Xurong Mei, Yuanyue Shen
Polyamines (PAs) participate in many plant growth and developmental processes, including fruit ripening. However, it is not clear whether PAs play a role in the ripening of strawberry (Fragaria ananassa), a model non-climacteric plant. Here, we found that the content of the PA spermine (Spm) increased more sharply after the onset of fruit coloration than did that of the PAs putrescine (Put) or spermidine (Spd). Spm dominance in ripe fruit resulted from abundant transcripts of a strawberry S-adenosyl-L-methionine decarboxylase gene (FaSAMDC), which encodes an enzyme that generates a residue needed for PA biosynthesis...
March 9, 2018: Plant Physiology
Johayra Simithy, Simone Sidoli, Benjamin A Garcia
The chromatin fiber is the control panel of eukaryotic cells. Chromatin is mostly composed of DNA, which contains the genetic instruction for cell phenotype, and histone proteins, which provide the scaffold for chromatin folding and part of the epigenetic inheritance. Histone writers/erasers "flag" chromatin regions by catalyzing/removing covalent histone post-translational modifications (PTMs). Histone PTMs chemically contribute to chromatin relaxation or compaction and recruit histone readers to modulate DNA readout...
March 7, 2018: Proteomics
Mark W Ruszczycky, Aoshu Zhong, Hung-Wen Liu
Radical SAM enzymes use S-adenosyl-l-methionine as an oxidant to initiate radical-mediated transformations that would otherwise not be possible with Lewis acid/base chemistry alone. These reactions are either redox neutral or oxidative leading to certain expectations regarding the role of SAM as either a reusable cofactor or the ultimate electron acceptor during each turnover. However, these expectations are frequently not realized resulting in fundamental questions regarding the redox handling and movement of electrons associated with these biological catalysts...
February 27, 2018: Natural Product Reports
Aimo Kannt, Sridharan Rajagopal, Sanjay Venkatachalapathi Kadnur, Juluri Suresh, Ravi Kanth Bhamidipati, Srinivasan Swaminathan, Mahanandeesha Siddappa Hallur, Rajendra Kristam, Ralf Elvert, Jörg Czech, Anja Pfenninger, Christine Rudolph, Herman Schreuder, Devaraj Venkatapura Chandrasekar, Vishal Subhash Mane, Swarnakumari Birudukota, Shama Shaik, Bharat Ravindra Zope, Raghunadha Reddy Burri, Niranjan Naranapura Anand, Manish Kumar Thakur, Manvi Singh, Reejuana Parveen, Saravanan Kandan, Ramesh Mullangi, Takeshi Yura, Ramachandraiah Gosu, Sven Ruf, Saravanakumar Dhakshinamoorthy
Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that catalyzes the transfer of a methyl group from the co-factor S-adenosyl-L-methionine (SAM) onto the substrate, nicotinamide (NA) to form 1-methyl-nicotinamide (MNA). Higher NNMT expression and MNA concentrations have been associated with obesity and type-2 diabetes. Here we report a small molecule analog of NA, JBSNF-000088, that inhibits NNMT activity, reduces MNA levels and drives insulin sensitization, glucose modulation and body weight reduction in animal models of metabolic disease...
February 26, 2018: Scientific Reports
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
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
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
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
Zhongyang Xu, Xiuyu Wang, Yanping Zheng
Ankylosing spondylitis (AS) is a chronic inflammatory arthritis and autoimmune disease, the etiology and pathogenesis of which remain largely unknown. In the present study, blood samples were harvested from patients with AS and from healthy volunteers as a normal control (NC) for RNA-sequencing. Differentially expressed genes (DEGs) in the AS group compared with the NC group were identified, and gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed...
February 2018: Experimental and Therapeutic Medicine
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
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
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
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 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
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
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
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
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
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
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
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