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S-adenosyl homocysteine

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https://www.readbyqxmd.com/read/29758262/s-adenosylhomocysteine-hydrolase-participates-in-dna-methylation-inheritance
#1
V K Chaithanya Ponnaluri, Pierre-Olivier Estève, Cristian I Ruse, Sriharsa Pradhan
DNA (cytosine-5) methyltransferase 1 (DNMT1) is essential for mammalian development and maintenance of DNA methylation following DNA replication in cells. The DNA methylation process generates S-adenosyl-L-homocysteine, a strong inhibitor of DNMT1. Here we report that S-adenosylhomocysteine hydrolase (SAHH/AHCY), the only mammalian enzyme capable of hydrolyzing S-adenosyl-L-homocysteine binds to DNMT1 during DNA replication. SAHH enhances DNMT1 activity in vitro, and its overexpression in mammalian cells led to hypermethylation of the genome, whereas its inhibition by adenosine periodate or siRNA mediated knock down resulted in hypomethylation of the genome...
May 11, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29747122/high-throughput-detection-of-deamidation-using-s-5-adenosyl-l-homocysteine-hydrolase-and-a-fluorogenic-reagent
#2
Brian M Murphy, Tarik J Ozumerzifon, Charles S Henry, Mark Cornell Manning
Deamidation of asparagine (Asn) residues is one of the most common chemical degradation pathways observed in proteins. This reaction must be understood and controlled in therapeutic drug candidates, as chemical changes can affect their efficacy and safety. The analytical tools available for detection of deamidation reaction products, such as isoaspartic acid residues, are either chromatographic or electrophoretic, and require MS detection for absolute identification of peaks. High-throughput measurement of protein degradation has typically been limited to probing the target's physical state using spectroscopic techniques...
May 1, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29687201/folate-promotes-s-adenosyl-methionine-reactions-and-the-microbial-methylation-cycle-and-boosts-ruminants-production-and-reproduction
#3
REVIEW
Imtiaz Hussain Raja Abbasi, Farzana Abbasi, Lamei Wang, Mohamed E Abd El Hack, Ayman A Swelum, Ren Hao, Junhu Yao, Yangchun Cao
Folate has gained significant attention due to its vital role in biological methylation and epigenetic machinery. Folate, or vitamin (B9 ), is only produced through a de novo mechanism by plants and micro-organisms in the rumen of mature animals. Although limited research has been conducted on folate in ruminants, it has been noted that ruminal synthesis could not maintain folate levels in high yielding dairy animals. Folate has an essential role in one-carbon metabolism and is a strong antiproliferative agent...
April 23, 2018: AMB Express
https://www.readbyqxmd.com/read/29679079/a-molecular-dynamics-simulation-study-decodes-the-zika-virus-ns5-methyltransferase-bound-to-sah-and-rna-analogue
#4
Chih-Hung Chuang, Shean-Jaw Chiou, Tian-Lu Cheng, Yeng-Tseng Wang
Since 2015, widespread Zika virus outbreaks in Central and South America have caused increases in microcephaly cases, and this acute problem requires urgent attention. We employed molecular dynamics and Gaussian accelerated molecular dynamics techniques to investigate the structure of Zika NS5 protein with S-adenosyl-L-homocysteine (SAH) and an RNA analogue, namely 7-methylguanosine 5'-triphosphate (m7GTP). For the binding motif of Zika virus NS5 protein and SAH, we suggest that the four Zika NS5 substructures (residue orders: 101-112, 54-86, 127-136 and 146-161) and the residues (Ser56, Gly81, Arg84, Trp87, Thr104, Gly106, Gly107, His110, Asp146, Ile147, and Gly148) might be responsible for the selectivity of the new Zika virus drugs...
April 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29619018/-s-adenosyl-l-homocysteine-hydrolase-inhibition-by-a-synthetic-nicotinamide-cofactor-biomimetic
#5
Lyn L Kailing, Daniela Bertinetti, Caroline E Paul, Tomasz Manszewski, Mariusz Jaskolski, Friedrich W Herberg, Ioannis V Pavlidis
S -adenosyl-L-homocysteine (SAH) hydrolases (SAHases) are involved in the regulation of methylation reactions in many organisms and are thus crucial for numerous cellular functions. Consequently, their dysregulation is associated with severe health problems. The SAHase-catalyzed reaction is reversible and both directions depend on the redox activity of nicotinamide adenine dinucleotide (NAD+ ) as a cofactor. Therefore, nicotinamide cofactor biomimetics (NCB) are a promising tool to modulate SAHase activity...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29531009/-communication-melatonin-hyperhomocysteinemia-thioretinaco-ozonide-adenosylmethionine-and-mitochondrial-dysfunction-in-aging-and-dementia
#6
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
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
#7
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
#8
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/29414770/homocysteine-regulates-fatty-acid-and-lipid-metabolism-in-yeast
#9
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 by-product 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 among others, is associated with a deregulation of lipid metabolism...
April 13, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29363853/disruption-of-the-methionine-cycle-and-reduced-cellular-gluthathione-levels-underlie-potex-potyvirus-synergism-in-nicotiana-benthamiana
#10
Swarnalok De, Gabriela Chavez-Calvillo, Matti Wahlsten, Kristiina Mäkinen
Infection caused by the synergistic interaction of two plant viruses is typically manifested by severe symptoms and increased accumulation of either virus. In potex-potyviral synergism, the potyviral RNA silencing suppressor helper component proteinase (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) are increased in Nicotiana benthamiana by Potato virus A (PVA; genus Potyvirus) HCPro expression...
January 24, 2018: Molecular Plant Pathology
https://www.readbyqxmd.com/read/29195982/high-resolution-mass-approach-to-characterize-refrigerated-black-truffles-stored-under-different-storage-atmospheres
#11
Edoardo Longo, Ksenia Morozova, Monica R Loizzo, Rosa Tundis, Sara Savini, Roberta Foligni, Massimo Mozzon, Daniel Martin-Vertedor, Matteo Scampicchio, Emanuele Boselli
Freshly harvested Tuber melanosporum samples were packed and stored at 4°C under reduced atmospheric pressure or modified atmosphere for four weeks. Multivariate analysis was employed to correlate the antioxidant power of the ethanolic extracts of the samples with the chemical composition determined by high resolution mass spectrometry. High performance liquid chromatography coupled with a coularray detector was applied to select the chemical species associated with the antioxidant power. Four classes of chemical compounds were investigated in more detail by a targeted approach: derivatives of glutathione, adenine (such as S-adenosyl-homocysteine), oxidized linoleic acid and ergosterol...
December 2017: Food Research International
https://www.readbyqxmd.com/read/29190095/mechanism-of-a-class-c-radical-s-adenosyl-l-methionine-thiazole-methyl-transferase
#12
Zhengan Zhang, Nilkamal Mahanta, Graham A Hudson, Douglas A Mitchell, Wilfred A van der Donk
The past decade has seen the discovery of four different classes of radical S-adenosylmethionine (rSAM) methyltransferases that methylate unactivated carbon centers. Whereas the mechanism of class A is well understood, the molecular details of methylation by classes B-D are not. In this study, we present detailed mechanistic investigations of the class C rSAM methyltransferase TbtI involved in the biosynthesis of the potent thiopeptide antibiotic thiomuracin. TbtI C-methylates a Cys-derived thiazole during posttranslational maturation...
December 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29155016/topical-administration-of-reversible-sahh-inhibitor-ameliorates-imiquimod-induced-psoriasis-like-skin-lesions-in-mice-via-suppression-of-tnf-%C3%AE-ifn-%C3%AE-induced-inflammatory-response-in-keratinocytes-and-t-cell-derived-il-17
#13
Ze-Min Lin, Meng Ma, Heng Li, Qing Qi, Yu-Ting Liu, Yu-Xi Yan, Yun-Fu Shen, Xiao-Qian Yang, Feng-Hua Zhu, Shi-Jun He, Wei Tang, Jian-Ping Zuo
DZ2002, a reversible S-adenosyl-l-homocysteine hydrolase (SAHH) inhibitor with immunosuppressive properties and potent therapeutic activity against various autoimmune diseases in mice. The present study was designed to characterize the potential therapeutic effects of DZ2002 on murine model of psoriasis and reveal the correlated mechanisms. In this report, we demonstrated that in vitro, DZ2002 significantly decreased the expression of pro-inflammatory cytokines and adhesion molecule including IL-1α, IL-1β, IL-6, IL-8, TNF-α and ICAM-1 by inhibiting the phosphorylation of p38 MAPK, ERK and JNK in TNF-α/IFN-γ-stimulated HaCaT human keratinocytes...
March 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29127188/epigenetically-mediated-inhibition-of-s-adenosylhomocysteine-hydrolase-and-the-associated-dysregulation-of-1-carbon-metabolism-in-nonalcoholic-steatohepatitis-and-hepatocellular-carcinoma
#14
Igor P Pogribny, Kostiantyn Dreval, Iryna Kindrat, Stepan Melnyk, Leandro Jimenez, Aline de Conti, Volodymyr Tryndyak, Marta Pogribna, Juliana Festa Ortega, S Jill James, Ivan Rusyn, Frederick A Beland
The substantial rise in the prevalence of nonalcoholic steatohepatitis (NASH), an advanced form of nonalcoholic fatty liver disease, and the strong association between NASH and the development of hepatocellular carcinoma indicate the urgent need for a better understanding of the underlying mechanisms. In the present study, by using the Stelic animal model of NASH and NASH-derived liver carcinogenesis, we investigated the role of the folate-dependent 1-carbon metabolism in the pathogenesis of NASH. We demonstrated that advanced NASH and NASH-related liver carcinogenesis are characterized by a significant dysregulation of 1-carbon homeostasis, with diminished expression of key 1-carbon metabolism genes, especially a marked inhibition of the S-adenosylhomocysteine hydrolase ( Ahcy) gene and an increased level of S-adenosyl-l-homocysteine (SAH)...
March 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29102113/different-activated-methyl-cycle-pathways-affect-the-pathogenicity-of-avian-pathogenic-escherichia-coli
#15
Da Xu, Jiakun Zuo, Zhaoguo Chen, Xiaolong Lv, Jiangang Hu, Xiaoka Wu, Kezong Qi, Rongsheng Mi, Yan Huang, Jingfeng Miao, Wei Jiang, Shaohui Wang, Chengming Wang, Xiangan Han
The activated methyl cycle (AMC) regulates the cellular levels of S-adenosyl-l-homocysteine (SAH) in bacteria, which plays a crucial role in bacterial pathogenicity. There are two AMC pathways in bacteria: one is a two-step reaction pathway (named the LuxS/Pfs pathway) in which LuxS and Pfs catalyze the conversion of SAH to l-homocysteine and autoinducer-2 (AI-2), and the other is a one-step reaction (named the SahH pathway) mediated by S-adenosyl-l-homocysteine hydrolase (SahH), which completes this cycle without producing AI-2...
November 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/29056905/hyperhomocysteinemia-suppressed-immunity-and-altered-oxidative-metabolism-caused-by-pathogenic-microbes-in-atherosclerosis-and-dementia
#16
REVIEW
Kilmer S McCully
Many pathogenic microorganisms have been demonstrated in atherosclerotic plaques and in cerebral plaques in dementia. Hyperhomocysteinemia, which is a risk factor for atherosclerosis and dementia, is caused by dysregulation of methionine metabolism secondary to deficiency of the allosteric regulator, adenosyl methionine. Deficiency of adenosyl methionine results from increased polyamine biosynthesis by infected host cells, causing increased activity of ornithine decarboxylase, decreased nitric oxide and peroxynitrate formation and impaired immune reactions...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29020412/emerging-role-of-one-carbon-metabolism-and-dna-methylation-enrichment-on-%C3%AE-containing-gabaa-receptor-expression-in-the-cerebellum-of-subjects-with-alcohol-use-disorders-aud
#17
Eleonora Gatta, James Auta, David P Gavin, Dulal K Bhaumik, Dennis R Grayson, Subhash C Pandey, Alessandro Guidotti
Background: Cerebellum is an area of the brain particularly sensitive to the effects of acute and chronic alcohol consumption. Alcohol exposure decreases cerebellar Purkinje cell output by increasing GABA release from Golgi cells onto extrasynaptic α6/δ-containing GABAA receptors located on glutamatergic granule cells. Here, we studied whether chronic alcohol consumption induces changes in GABAA receptor subunit expression and whether these changes are associated with alterations in epigenetic mechanisms via DNA methylation...
December 1, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28984387/gene-expression-differences-in-the-methionine-remethylation-and-transsulphuration-pathways-under-methionine-restriction-and-recovery-with-d-l-methionine-or-d-l-hmtba-in-meat-type-chickens
#18
S E Aggrey, F González-Cerón, R Rekaya, Y Mercier
This study examined the molecular mechanisms of methionine pathways in meat-type chickens where birds were provided with a diet deficient in methionine from 3 to 5 weeks of age. The birds on the deficient diet were then provided with a diet supplemented with either D,L-methionine or D,L-HMTBA from 5 to 7 weeks. The diet of the control birds was supplemented with L-methionine from hatch till 7 weeks of age. We studied the mRNA expression of methionine adenosyltransferase 1, alpha, methionine adenosyltransferase 1, beta, 5-methyltetrahydrofolate-homocysteine methyltransferase, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase, betaine-homocysteine S-methyltransferase, glycine N-methyltransferase, S-adenosyl-L-homocysteine hydrolase and cystathionine beta synthase genes in the liver, duodenum, Pectoralis (P...
February 2018: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28959863/-purification-and-characterization-of-s-adenosyl-l-methionine-uroporphyrinogen-%C3%A2-methyltransferase-from-rhodobacter-capsulatus-sb1003
#19
Jie Kang, Huan Fang, Huina Dong, Wenjun Song, Dawei Zhang
Biosynthesis of vitamin B₁₂ (VB₁₂) requires the methylation at positions C-2 and C-7 of the precursor uroporphyrinogen Ⅲ (urogen Ⅲ) to precorrin-2 by S-adenosyl-L-methionine uroporphyrinogen Ⅲ methyltransferase (SUMT), which is a potential bottleneck step. Most of SUMTs are inhibited by urogen Ⅲ and by-product S-adenosyl-L-homocysteine (SAH). In order to mine an SUMT that lacks such an inhibitory property to drive greater flux through the VB₁₂ biosynthetic pathway, we cloned two SUMT genes (RCcobA1, RCcobA2) from Rhodobacter capsulatus SB1003 and expressed them in Escherichia coli BL21 (DE3)...
January 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/28933241/characterization-of-human-s-adenosyl-homocysteine-hydrolase-in-vitro-and-identification-of-its-potential-inhibitors
#20
Weiwei Hao, Yanhua Li, Qiuli Shan, Tian Han, Wencheng Li, Sheng He, Kongkai Zhu, Yumei Li, Xiaojun Tan, Jinsong Gu
Human S-adenosyl-homocysteine hydrolase (SAHH, E.C.3.3.1.1) has been considered to be an attractive target for the design of medicines to treat human disease, because of its important role in regulating biological methylation reactions to catalyse the reversible hydrolysis of S-adenosylhomocysteine (SAH) to adenosine (Ado) and l-homocysteine (Hcy). In this study, SAHH protein was successfully cloned and purified with optimized, Pichia pastoris (P. pastoris) expression system. The biological activity results revealed that, among the tested compounds screened by ChemMapper and SciFinder Scholar, 4-(3-hydroxyprop-1-en-1-yl)-2-methoxyphenol (coniferyl alcohol, CAS: 458-35-5, ZINC: 12359045) exhibited the highest inhibition against rSAHH (IC50= 34 nM)...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
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