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Methionine Adenosyltransferase

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https://www.readbyqxmd.com/read/29943221/newborn-screening-for-homocystinurias-recent-recommendations-versus-current-practice
#1
R Keller, P Chrastina, M Pavlíková, S Gouveia, A Ribes, S Kölker, H J Blom, M R Baumgartner, J Bártl, C Dionisi Vici, F Gleich, A A Morris, V Kožich, M Huemer, I Barić, T Ben-Omran, J Blasco-Alonso, M A Bueno Delgado, C Carducci, M Cassanello, R Cerone, M L Couce, E Crushell, C Delgado Pecellin, E Dulin, M Espada, G Ferino, R Fingerhut, I Garcia Jimenez, I Gonzalez Gallego, Y González-Irazabal, G Gramer, M J Juan Fita, E Karg, J Klein, V Konstantopoulou, G la Marca, E Leão Teles, V Leuzzi, F Lilliu, R M Lopez, A M Lund, P Mayne, S Meavilla, S J Moat, J G Okun, E Pasquini, C Pedron-Giner, G Z Racz, M A Ruiz Gomez, L Vilarinho, R Yahyaoui, M Zerjav Tansek, R H Zetterström, M Zeyda
PURPOSE: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations. METHODS: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8)...
June 15, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29939201/modulation-of-dietary-methionine-intake-elicits-potent-yet-distinct-anticancer-effects-on-primary-versus-metastatic-tumors
#2
Isabelle R Miousse, Julia Tobacyk, Charles M Quick, Azemat Jamshidi-Parsian, Charles M Skinner, Rajshekhar Kore, Stepan B Melnyk, Kristy R Kutanzi, Fen Xia, Robert J Griffin, Igor Koturbash
Methionine dependency describes the characteristic rapid in vitro death of most tumor cells in the absence of methionine. Combining chemotherapy with dietary methionine deprivation (MDD) at tolerable levels has vast potential in tumor treatment; however, it is limited by MDD-induced toxicity during extended deprivation. Recent advances in imaging and irradiation delivery have created the field of stereotactic body radiotherapy (SBRT), where fewer large-dose fractions delivered in less time result in increased local-tumor control, which could be maximally synergistic with an MDD short course...
June 23, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29924862/identification-of-hepatic-protein-protein-interaction-targets-for-betaine-homocysteine-s-methyltransferase
#3
Francisco Garrido, María Pacheco, Rocío Vargas-Martínez, Roberto Velasco-García, Inmaculada Jorge, Horacio Serrano, Francisco Portillo, Jesús Vázquez, María Ángeles Pajares
Protein-protein interactions are an important mechanism for the regulation of enzyme function allowing metabolite channeling, crosstalk between pathways or the introduction of post-translational modifications. Therefore, a number of high-throughput studies have been carried out to shed light on the protein networks established under different pathophysiological settings. Surprisingly, this type of information is quite limited for enzymes of intermediary metabolism such as betaine homocysteine S-methyltransferase, despite its high hepatic abundancy and its role in homocysteine metabolism...
2018: PloS One
https://www.readbyqxmd.com/read/29780898/sumoylation-and-phosphorylation-cross-talk-in-hepatocellular-carcinoma
#4
REVIEW
Maria Lauda Tomasi, Komal Ramani
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. The large spectrum of protein post-translational modification (PTM) includes numerous critical signaling events that occur during neoplastic transformation. PTMs occur to nearly all proteins and increase the functional diversity of proteins. We have reviewed the role of two major PTMs, SUMOylation and phosphorylation, in the altered signaling of key players in HCC...
2018: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29777905/coupling-of-the-polyamine-and-iron-metabolism-pathways-in-the-regulation-of-proliferation-mechanistic-links-to-alterations-in-key-polyamine-biosynthetic-and-catabolic-enzymes
#5
Darius J R Lane, Dong-Hun Bae, Aritee R Siafakas, Yohan Suryo Rahmanto, Lina Al-Akra, Patric J Jansson, Robert A Casero, Des R Richardson
Many biological processes result from the coupling of metabolic pathways. Considering this, proliferation depends on adequate iron and polyamines, and although iron-depletion impairs proliferation, the metabolic link between iron and polyamine metabolism has never been thoroughly investigated. This is important to decipher, as many disease states demonstrate co-dysregulation of iron and polyamine metabolism. Herein, for the first time, we demonstrate that cellular iron levels robustly regulate 13 polyamine pathway proteins...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29749642/a-novel-mechanism-of-the-m1-m2-methionine-adenosyltransferase-switch-mediated-hepatocellular-carcinoma-metastasis
#6
Ruizhi Wang, Yi Jin, Xue-Hua Yao, Wenzhe Fan, Jiang Zhang, Yihai Cao, Jiaping Li
Hepatocellular carcinoma (HCC) manifests as a highly metastatic cancer with extremely poor prognosis. However, mechanisms underlying metastasis of HCC are not fully understood. Here, we showed that switching gene expression from MAT1A to MAT2A (M1-M2 switch) promoted cancer invasion and metastasis. Reversion of the M1-M2 switch repressed, whereas enhancing the M1-M2 switch promoted the ability of HCC cells to metastasize. Moreover, we provided clinical data showing that tipping the balance between MAT1A and MAT2A expression correlated with increased metastasis and inferior recurrence-free survival in HCC patients...
May 10, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29733835/mechanisms-of-mafg-dysregulation-in-cholestatic-liver-injury-and-development-of-liver-cancer
#7
Ting Liu, Heping Yang, Wei Fan, Jian Tu, Tony W H Li, Jiaohong Wang, Hong Shen, JinWon Yang, Ting Xiong, Justin Steggerda, Zhenqiu Liu, Mazen Noureddin, Stephanie S Maldonado, Alagappan Annamalai, Ekihiro Seki, José M Mato, Shelly C Lu
BACKGROUND & AIMS: MAF bZIP transcription factor G (MAFG) is activated by the farnesoid X receptor (FXR) to repress bile acid synthesis. However, expression of MAFG increases during cholestatic liver injury in mice and in cholangiocarcinomas. MAFG interacts directly with methionine adenosyltransferase 1A (MAT1A) and other transcription factors at the E-box element to repress transcription. We studied mechanisms of MAFG upregulation in cholestatic tissues and the pathways by which S-adenosylmethionine (SAMe) and ursodeoxycholic acid (UDCA) prevent the increase in MAFG expression...
May 4, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29572390/methionine-adenosyltransferase4-mediates-dna-and-histone-methylation
#8
Jingjing Meng, Lishuan Wang, Jingyi Wang, Xiaowen Zhao, Jinkui Cheng, Wenxiang Yu, Dan Jin, Qing Li, Zhizhong Gong
DNA and histone methylation coregulate heterochromatin formation and gene silencing in animals and plants. To identify factors involved in maintaining gene silencing, we conducted a forward genetic screen for mutants that release the silenced transgene Pro35S::NEOMYCIN PHOSPHOTRANSFERASE II in the transgenic Arabidopsis ( Arabidopsis thaliana ) line L119 We identified MAT4/SAMS3/MTO3/AT3G17390 , which encodes methionine (Met) adenosyltransferase 4 (MAT4)/ S -adenosyl-Met synthetase 3 that catalyzes the synthesis of S -adenosyl-Met (SAM) in the one-carbon metabolism cycle...
June 2018: Plant Physiology
https://www.readbyqxmd.com/read/29527286/phenylethynyl-substituted-heterocycles-inhibit-cyclin-d1-and-induce-the-expression-of-cyclin-dependent-kinase-inhibitor-p21-wif1-cip1-in-colorectal-cancer-cells
#9
Vitaliy M Sviripa, Liliia M Kril, Wen Zhang, Yanqi Xie, Przemyslaw Wyrebek, Larissa Ponomareva, Xifu Liu, Yaxia Yuan, Chang-Guo Zhan, David S Watt, Chunming Liu
Fluorinated, phenylethynyl-substituted heterocycles that possessed either an N -methylamino or N,N -dimethylamino group attached to heterocycles including pyridines, indoles, 1 H -indazoles, quinolines, and isoquinolines inhibited the proliferation of LS174T colon cancer cells in which the inhibition of cyclin D1 and induction of the cyclin-dependent kinase inhibitor-1 ( i.e ., p21Wif1/Cip1 ) served as a readout for antineoplastic activity at a cellular level. On a molecular level, these agents, particularly 4-((2,6-difluorophenyl)ethynyl)- N -methylisoquinolin-1-amine and 4-((2,6-difluorophenyl)ethynyl)- N , N -dimethylisoquinolin-1-amine, bound and inhibited the catalytic subunit of methionine S-adenosyltransferase-2 (MAT2A)...
2018: MedChemComm
https://www.readbyqxmd.com/read/29448301/histological-expression-of-methionine-adenosyl-transferase-mat-2a-as-a-post-surgical-prognostic-surrogate-in-patients-with-hepatocellular-carcinoma
#10
Jihyun An, Seong Kyun Na, Ju Hyun Shim, Yang Soon Park, Mi Jung Jun, Joo Ho Lee, Gi-Won Song, Hac Chu Lee, Eunsil Yu
BACKGROUND AND OBJECTIVES: Deregulation of methionine adenosyltransferase (MAT) is involved in hepatocarcinogenesis. This study aimed to investigate the prognostic implications of the level of histological MAT1A and MAT2A in patients with resected hepatocellular carcinoma (HCC). METHODS: A total of 210 patients with HCC who underwent curative resection between 2004 and 2011 were included. The levels of MAT proteins were immunohistochemically measured. RESULTS: MAT1A and MAT2A were over-expressed in 134 (63...
April 2018: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29440907/methionine-adenosyltransferase-i-iii-deficiency-beyond-the-central-nervous-system-manifestations
#11
Marwan Nashabat, Sultan Al-Khenaizan, Majid Alfadhel
Methionine adenosyltransferase (MAT) I/III deficiency (OMIM # 250850) is caused by a mutation in MAT1A , which encodes the two hepatic MAT isozymes I and III. With the implementation of newborn screening program to discover hypermethioninemia due to cystathionine beta-synthase deficiency, more cases are being discovered. While the majority of patients are asymptomatic, some might have central nervous system (CNS) and extra-CNS manifestations. Although neurologic manifestations and demyelination have been correlated to MAT deficiency in many reported cases, none of the previous reports focused on extra-CNS manifestations associated with the disease...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29353869/lipofection-of-sirna-into-bovine-8-16-cell-stage-embryos-using-zona-removal-and-the-well-of-the-well-culture-system
#12
Shuntaro Ikeda, Miki Sugimoto, Shinichi Kume
Bovine preimplantation embryos exhibit dramatic biological changes between before and after the 8-16-cell stage. Here we report a simple lipofection method to transfect siRNA into bovine 8-16-cell stage embryos using zona removal and the well-of-the-well (WOW) culture system. Bovine one-cell embryos produced in vitro were freed from the zona pellucida and cultured up to the 8-16-cell stage in WOW dishes. The 8-16-cell embryos were lipofected with siRNA and the transfection efficiency was assessed at 48 h of transfection...
April 13, 2018: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/29344166/identification-and-functional-analysis-of-risk-related-micrornas-for-the-prognosis-of-patients-with-bladder-urothelial-carcinoma
#13
Ji Gao, Hongyan Li, Lei Liu, Lide Song, Yanting Lv, Yuping Han
The aim of the present study was to investigate risk-related microRNAs (miRs) for bladder urothelial carcinoma (BUC) prognosis. Clinical and microRNA expression data downloaded from the Cancer Genome Atlas were utilized for survival analysis. Risk factor estimation was performed using Cox's proportional regression analysis. A microRNA-regulated target gene network was constructed and presented using Cytoscape. In addition, the Database for Annotation, Visualization and Integrated Discovery was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment, followed by protein-protein interaction (PPI) network analysis...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29262316/s-adenosylmethionine-synthesis-is-regulated-by-selective-n-6-adenosine-methylation-and-mrna-degradation-involving-mettl16-and-ythdc1
#14
Hiroki Shima, Mitsuyo Matsumoto, Yuma Ishigami, Masayuki Ebina, Akihiko Muto, Yuho Sato, Sayaka Kumagai, Kyoko Ochiai, Tsutomu Suzuki, Kazuhiko Igarashi
S-adenosylmethionine (SAM) is an important metabolite as a methyl-group donor in DNA and histone methylation, tuning regulation of gene expression. Appropriate intracellular SAM levels must be maintained, because methyltransferase reaction rates can be limited by SAM availability. In response to SAM depletion, MAT2A, which encodes a ubiquitous mammalian methionine adenosyltransferase isozyme, was upregulated through mRNA stabilization. SAM-depletion reduced N6 -methyladenosine (m6 A) in the 3' UTR of MAT2A...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29225734/-pdrg1-at-the-interface-between-intermediary-metabolism-and-oncogenesis
#15
REVIEW
María Ángeles Pajares
PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damage-regulated gene 1 ( PDRG1 ) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase II complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear...
November 26, 2017: World Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29170720/methionine-adenosyltransferases-in-liver-health-and-diseases
#16
Komal Ramani, Shelly C Lu
Methionine adenosyltransferases (MATs) are essential for cell survival because they catalyze the biosynthesis of the biological methyl donor S-adenosylmethionine (SAMe) from methionine and adenosine triphosphate (ATP). Mammalian cells express two genes, MAT1A and MAT2A , which encode two MAT catalytic subunits, α1 and α2, respectively. The α1 subunit organizes into dimers (MATIII) or tetramers (MATI). The α2 subunit is found in the MATII isoform. A third gene MAT2B , encodes a regulatory subunit β, that regulates the activity of MATII by lowering the inhibition constant (Ki ) for SAMe and the Michaelis constant (Km ) for methionine...
September 2017: Liver Research
https://www.readbyqxmd.com/read/29142482/-s-adenosyl-l-methionine-towards-hepatitis-c-virus-expression-need-to-consider-s-adenosyl-l-methionine-s-chemistry-physiology-and-pharmacokinetics
#17
Dimitrios Tsikas, Erik Hanff, Alexander Bollenbach
S -Adenosyl-L-methionine (SAM) is a cofactor serving as a methyl donor in numerous enzymatic reactions. It has been reported that SAM has the potential to modify antioxidant-enzymes, glutathione-biosynthesis and methionine adenosyltransferases-1/2 in hepatitis C virus -expressing cells at millimolar concentrations. The efficacy of SAM at micromolar concentrations and the underlying mechanisms remain to be demonstrated.
October 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29141455/methionine-adenosyltransferases-in-cancers-mechanisms-of-dysregulation-and-implications-for-therapy
#18
Lauren Y Maldonado, Diana Arsene, José M Mato, Shelly C Lu
Methionine adenosyltransferase genes encode enzymes responsible for the biosynthesis of S-adenosylmethionine, the principal biological methyl donor and precursor of polyamines and glutathione. Mammalian cells express three genes - MAT1A, MAT2A, and MAT2B - with distinct expression and functions. MAT1A is mainly expressed in the liver and maintains the differentiated states of both hepatocytes and bile duct epithelial cells. Conversely, MAT2A and MAT2B are widely distributed in non-parenchymal cells of the liver and extrahepatic tissues...
January 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29133280/mat2a-promotes-porcine-adipogenesis-by-mediating-h3k27me3-at-wnt10b-locus-and-repressing-wnt-%C3%AE-catenin-signaling
#19
Cunzhen Zhao, Haigang Wu, Naren Qimuge, Weijun Pang, Xiao Li, Guiyan Chu, Gongshe Yang
Methionine adenosyltransferase (MAT) is a critical biological enzyme and that can catalyze L-met and ATP to form S-adenosylmethionine (SAM), which is acted as a biological methyl donor in transmethylation reactions involving histone methylation. However, the regulatory effect of methionine adenosyltransferase2A (MAT2A) and its associated methyltransferase activity on adipogenesis is still unclear. In this study, we investigate the effect of MAT2A on adipogenesis and its potential mechanism on histone methylation during porcine preadipocyte differentiation...
February 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29111970/complementation-of-a-metk-deficient-e-coli-strain-with-heterologous-adomet-synthetase-genes
#20
Gwenn G Parungao, Mojun Zhao, Qinzhe Wang, Stephen P Zano, Ronald E Viola, Robert M Blumenthal
S-adenosyl-l-methionine (AdoMet) is an essential metabolite, playing a wide variety of metabolic roles. The enzyme that produces AdoMet from l-methionine and ATP (methionine adenosyltransferase, MAT) is thus an attractive target for anti-cancer and antimicrobial agents. It would be very useful to have a system that allows rapid identification of species-specific inhibitors of this essential enzyme. A previously generated E. coli strain, lacking MAT (∆metK) but containing a heterologous AdoMet transporter, was successfully complemented with heterologous metK genes from several bacterial pathogens, as well as with MAT genes from a fungal pathogen and Homo sapiens...
December 2017: Microbiology
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