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S-adenosyl homocysteine

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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/28701466/methionine-synthase-is-localized-to-the-nucleus-in-pichia-pastoris-and-candida-albicans-and-to-the-cytoplasm-in-saccharomyces-cerevisiae
#3
Umakant Sahu, Hunsur R Vinod Kumar, Shankar S Kapnoor, Raghu Bhagavat, Nagasuma Chandra, Pundi N Rangarajan
Methionine synthase (MS) catalyzes methylation of homocysteine, the last step in the biosynthesis of methionine, which is essential for the regeneration of tetrahydrofolate and biosynthesis of S-adenosyl methionine. Here, we report that MS is localized to the nucleus of Pichia pastoris and Candida albicans but cytoplasmic in Saccharomyces cerevisiaeP. pastoris strain carrying a deletion of MET6 gene encoding MS (Ppmet6) exhibits methionine as well as adenine auxotrophy indicating that MS is required for methionine as well as adenine biosynthesis...
July 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28660490/arjunolic-acid-improves-the-serum-level-of-vitamin-b12-and-folate-in-the-process-of-the-attenuation-of-arsenic-induced-uterine-oxidative-stress
#4
Moulima Maity, Hasina Perveen, Moumita Dash, Suryashis Jana, Shamima Khatun, Arindam Dey, Amit Kumar Mandal, Sandip Chattopadhyay
Continuation of prolonged treatment against arsenicosis with conventional chelating therapy is a global challenge. The present study was intended to evaluate the defensive effect of arjunolic acid against arsenic-induced oxidative stress and female reproductive dysfunction. Wistar strain adult female rats were given sodium arsenite (10 mg/kg body weight) in combination with arjunolic acid (10 mg/kg body weight) orally for two estrous cycles. Electrozymographic analysis explored that arjunolic acid co-treatment counteracted As(3+)-induced ROS production in uterine tissue by stimulating the activities of endogenous enzymatic antioxidants...
June 28, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28629859/s-adenosyl-l-homocysteine-hydrolase-from-a-hyperthermophile-thermotoga-maritima-is-expressed-in-escherichia-coli-in-inactive-form-biochemical-and-structural-studies
#5
Krzysztof Brzezinski, Justyna Czyrko, Joanna Sliwiak, Edyta Nalewajko-Sieliwoniuk, Mariusz Jaskolski, Boguslaw Nocek, Zbigniew Dauter
Thermotoga maritima is a hyperthermophilic bacterium but its genome encodes a number of archaeal proteins including S-adenosyl-L-homocysteine hydrolase (SAHase), which regulates cellular methylation reactions. The question of proper folding and activity of proteins of extremophilic origin is an intriguing problem. When expressed in E.coli and purified (as a homotetramer) at room temperature, the hyperthermophilic SAHase from T.maritima was inactive. ITC study indicated that the protein undergoes heat-induced conformational changes, and enzymatic activity assays demonstrated that these changes are required to attain enzymatic activity...
June 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28623948/one-carbon-metabolism-cognitive-impairment-and-csf-measures-of-alzheimer-pathology-homocysteine-and-beyond
#6
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/28575637/folic-acid-attenuates-homocysteine-and-enhances-antioxidative-capacity-in-atherosclerotic-rats
#7
Shanshan Cui, Wen Li, Xin Lv, Pengyan Wang, Guowei Huang, Yuxia Gao
Atherosclerosis is a chronic disease that can seriously endanger human life. Folic acid supplementation modulates several disorders, including atherosclerosis, via its antiapoptotic and antioxidative properties. This study investigated whether folic acid alleviates atherogenesis by restoring homocysteine levels and antioxidative capacity in atherosclerosis Wistar rats. To this end, 28 Wistar rats were randomly divided into 4 groups (7 rats/group) as follows: (i) wild-type group, fed only the AIN-93 semi-purified rodent diet (folic acid: 2...
June 2, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28512574/crystallographic-and-saxs-studies-of-s-adenosyl-l-homocysteine-hydrolase-from-bradyrhizobium-elkanii
#8
Tomasz Manszewski, Kamil Szpotkowski, Mariusz Jaskolski
S-Adenosyl-l-homocysteine hydrolase (SAHase) from the symbiotic bacterium Bradyrhizobium elkanii (BeSAHase) was crystallized in four ligand complexes with (i) mixed adenosine (Ado) and cordycepin (Cord; 3'-deoxyadenosine), (ii) adenine (Ade), (iii) Ado and (iv) mixed 2'-deoxyadenosine (2'-dAdo) and Ade. The crystal structures were solved at resolutions of 1.84, 1.95, 1.95 and 1.54 Å, respectively. Only the Ade complex crystallized with a dimer in the asymmetric unit, while all of the other complexes formed a crystallographically independent tetrameric assembly...
May 1, 2017: IUCrJ
https://www.readbyqxmd.com/read/28484204/hydrogen-sulfide-improves-cardiomyocyte-function-in-a-cardiac-arrest-model
#9
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
#10
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/28461153/a-coupled-photometric-assay-for-characterization-of-s-adenosyl-l-homocysteine-hydrolases-in-the-physiological-hydrolytic-direction
#11
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/28435838/thiol-trapping-and-metabolic-redistribution-of-sulfur-metabolites-enable-cells-to-overcome-cysteine-overload
#12
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/28422052/folic-acid-reduces-tau-phosphorylation-by-regulating-pp2a-methylation-in-streptozotocin-induced-diabetic-mice
#13
Miaoyan Zheng, Chen Zou, Mengyue Li, Guowei Huang, Yuxia Gao, Huan Liu
High incidence rate of Alzheimer's disease (AD) is observed in patients with type 2 diabetes. Aggregated β-amyloid (Aβ) and hyperphosphorylated tau are the hallmarks of AD. Hyperphosphorylated tau has been detected in diabetic animals as well as in diabetic patients. Folates mediate the transfer of one carbon unit, required in various biochemical reactions. The effect of folate on tau phosphorylation in diabetic models still remains unknown. In this study, we investigated the effect and mechanism of folic acid on hyperphosphorylation of tau in streptozotocin (STZ)-induced diabetic mice...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28421128/a-clinically-relevant-variant-of-the-human-hydrogen-sulfide-synthesizing-enzyme-cystathionine-%C3%AE-synthase-increased-co-reactivity-as-a-novel-molecular-mechanism-of-pathogenicity
#14
João B Vicente, Henrique G Colaço, Francesca Malagrinò, Paulo E Santo, André Gutierres, Tiago M Bandeiras, Paula Leandro, José A Brito, Alessandro Giuffrè
The human disease classical homocystinuria results from mutations in the gene encoding the pyridoxal 5'-phosphate- (PLP-) dependent cystathionine β-synthase (CBS), a key enzyme in the transsulfuration pathway that controls homocysteine levels, and is a major source of the signaling molecule hydrogen sulfide (H2S). CBS activity, contributing to cellular redox homeostasis, is positively regulated by S-adenosyl-L-methionine (AdoMet) but fully inhibited upon CO or NO• binding to a noncatalytic heme moiety. Despite extensive studies, the molecular basis of several pathogenic CBS mutations is not yet fully understood...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28369960/chronic-alcohol-exposure-differentially-alters-one-carbon-metabolism-in-rat-liver-and-brain
#15
James Auta, Huaibo Zhang, Subhash C Pandey, Alessandro Guidotti
BACKGROUND: Epigenetic mechanisms such as DNA methylation play an important role in regulating the pathophysiology of alcoholism. Chronic alcohol exposure leads to behavioral changes as well as decreased expression of genes associated with synaptic plasticity. In the liver, it has been documented that chronic alcohol exposure impairs methionine synthase (Ms) activity leading to a decrease in S-adenosyl methionine/S-adenosyl homocysteine (SAM/SAH) ratio which results in DNA hypomethylation; however, it is not known whether similar alterations of SAM and SAH levels are also produced in brain...
June 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28345600/the-structure-of-zika-virus-ns5-reveals-a-conserved-domain-conformation
#16
Boxiao Wang, Xiao-Feng Tan, Stephanie Thurmond, Zhi-Min Zhang, Asher Lin, Rong Hai, Jikui Song
The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one of the two alternative conformations of flavivirus NS5 proteins. The activity of this NS5 protein is verified through a de novo RdRp assay on a subgenomic ZIKV RNA template. Importantly, our structural analysis leads to the identification of a potential drug-binding site of ZIKV NS5, which might facilitate the development of novel antivirals for ZIKV...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28238725/functional-and-structural-analysis-of-programmed-c-methylation-in-the-biosynthesis-of-the-fungal-polyketide-citrinin
#17
Philip A Storm, Dominik A Herbst, Timm Maier, Craig A Townsend
Fungal polyketide synthases (PKSs) are large, multidomain enzymes that biosynthesize a wide range of natural products. A hallmark of these megasynthases is the iterative use of catalytic domains to extend and modify a series of enzyme-bound intermediates. A subset of these iterative PKSs (iPKSs) contains a C-methyltransferase (CMeT) domain that adds one or more S-adenosylmethionine (SAM)-derived methyl groups to the carbon framework. Neither the basis by which only specific positions on the growing intermediate are methylated ("programming") nor the mechanism of methylation are well understood...
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28135697/colorimetric-detection-of-endogenous-hydrogen-sulfide-production-in-living-cells
#18
Yong Jin Ahn, Young Ju Lee, Jaemyeon Lee, Doyeon Lee, Hun-Kuk Park, Gi-Ja Lee
Hydrogen sulfide (H2S) has received great attention as a third gaseous signal transmitter, following nitric oxide and carbon monoxide. In particular, H2S plays an important role in the regulation of cancer cell biology. Therefore, the detection of endogenous H2S concentrations within biological systems can be helpful to understand the role of gasotransmitters in pathophysiology. Although a simple and inexpensive method for the detection of H2S has been developed, its direct and precise measurement in living cells remains a challenge...
April 15, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/27934872/structural-analysis-of-glycine-sarcosine-n-methyltransferase-from-methanohalophilus-portucalensis-reveals-mechanistic-insights-into-the-regulation-of-methyltransferase-activity
#19
Yi-Ru Lee, Te-Sheng Lin, Shu-Jung Lai, Mu-Sen Liu, Mei-Chin Lai, Nei-Li Chan
Methyltransferases play crucial roles in many cellular processes, and various regulatory mechanisms have evolved to control their activities. For methyltransferases involved in biosynthetic pathways, regulation via feedback inhibition is a commonly employed strategy to prevent excessive accumulation of the pathways' end products. To date, no biosynthetic methyltransferases have been characterized by X-ray crystallography in complex with their corresponding end product. Here, we report the crystal structures of the glycine sarcosine N-methyltransferase from the halophilic archaeon Methanohalophilus portucalensis (MpGSMT), which represents the first structural elucidation of the GSMT methyltransferase family...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27879050/structural-studies-of-protein-arginine-methyltransferase-2-reveal-its-interactions-with-potential-substrates-and-inhibitors
#20
Vincent Cura, Nils Marechal, Nathalie Troffer-Charlier, Jean-Marc Strub, Matthijs J van Haren, Nathaniel I Martin, Sarah Cianférani, Luc Bonnefond, Jean Cavarelli
PRMT2 is the less-characterized member of the protein arginine methyltransferase family in terms of structure, activity, and cellular functions. PRMT2 is a modular protein containing a catalytic Ado-Met-binding domain and unique Src homology 3 domain that binds proteins with proline-rich motifs. PRMT2 is involved in a variety of cellular processes and has diverse roles in transcriptional regulation through different mechanisms depending on its binding partners. PRMT2 has been demonstrated to have weak methyltransferase activity on a histone H4 substrate, but its optimal substrates have not yet been identified...
January 2017: FEBS Journal
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