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Methionine Adenosyltransferase

Rebecca Keller, Petr Chrastina, Markéta Pavlíková, Sofía Gouveia, Antonia Ribes, Stefan Kölker, Henk J Blom, Matthias R Baumgartner, Josef Bártl, Carlo Dionisi-Vici, Florian Gleich, Andrew A Morris, Viktor Kožich, Martina Huemer, Ivo Barić, Tawfeq Ben-Omran, Javier Blasco-Alonso, Maria A Bueno Delgado, Claudia Carducci, Michela Cassanello, Roberto Cerone, Maria Luz Couce, Ellen Crushell, Carmen Delgado Pecellin, Elena Dulin, Mercedes Espada, Giulio Ferino, Ralph Fingerhut, Immaculada Garcia Jimenez, Immaculada Gonzalez Gallego, Yolanda González-Irazabal, Gwendolyn Gramer, Maria Jesus Juan Fita, Eszter Karg, Jeanette Klein, Vassiliki Konstantopoulou, Giancarlo la Marca, Elisa Leão Teles, Vincenzo Leuzzi, Franco Lilliu, Rosa Maria Lopez, Allan M Lund, Philip Mayne, Silvia Meavilla, Stuart J Moat, Jürgen G Okun, Elisabeta Pasquini, Consuélo Carmen Pedron-Giner, Gabor Zoltan Racz, Maria Angeles Ruiz Gomez, Laura Vilarinho, Raquel Yahyaoui, Moja Zerjav Tansek, Rolf H Zetterström, Maximilian 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)...
January 2019: Journal of Inherited Metabolic Disease
Jing Bai, Yuanyuan Gao, Linjiao Chen, Qianqian Yin, Fangzhou Lou, Zhikai Wang, Zhenyao Xu, Hong Zhou, Qun Li, Wei Cai, Yang Sun, Liman Niu, Hong Wang, Zhenquan Wei, Shaoyong Lu, Aiwu Zhou, Jian Zhang, Honglin Wang
BACKGROUND: Psoriasis is a common chronic inflammatory skin disease which lacks effective strategies for the treatment. Natural compounds with biological activities are good tools to identify new targets with therapeutic potentials. Acetyl-11-keto-β-boswellic acid (AKBA) is the most bioactive ingredient of boswellic acids, a group of compounds with anti-inflammatory and anti-cancer properties. Target identification of AKBA and metabolomics analysis of psoriasis helped to elucidate the molecular mechanism underlying its effect, and provide new target(s) to treat the disease...
December 24, 2018: EBioMedicine
Dahui Wang, Dechao Li, Gaochuan Zhang, Chonglong Wang, Gongyuan Wei
The por1 gene encoding one of the mitochondrial porin channels in C. utilis CCTCC M 209298 was disrupted using a homologous recombination method. The co-production of S-adenosylmethionine (SAM) and glutathione (GSH) in the mutant C. utilis Δpor1 increased by 34.9% and 25.1%, respectively, during batch and fed-batch fermentation, relative to the parental strain. The average oxygen consumption rate, activities of key enzymes involved in SAM and GSH biosynthesis, levels of intracellular cofactors such as NADH and ATP, and carbon fluxes of key metabolites were compared between the parental strain and the Δpor1 mutant...
December 13, 2018: Journal of Biotechnology
M Kalim Akhtar, Dhanya Vijay, Saima Umbreen, Chris J McLean, Yizhi Cai, Dominic J Campopiano, Gary J Loake
Methylated chemicals are widely used as key intermediates for the syntheses of pharmaceuticals, fragrances, flavors, biofuels and plastics. In nature, the process of methylation is commonly undertaken by a super-family of S-adenosyl methionine-dependent enzymes known as methyltransferases. Herein, we describe a novel high throughput enzyme-coupled assay for determining methyltransferase activites. Adenosylhomocysteine nucleosidase, xanthine oxidase, and horseradish peroxidase enzymes were shown to function in tandem to generate a fluorescence signal in the presence of S-adenosyl-L-homocysteine and Amplex Red (10-acetyl-3,7-dihydroxyphenoxazine)...
2018: Frontiers in Bioengineering and Biotechnology
Jun Kido, Takaaki Sawada, Ken Momosaki, Yosuke Suzuki, Hiroyuki Uetani, Mika Kitajima, Hiroshi Mitsubuchi, Kimitoshi Nakamura, Shirou Matsumoto
Methionine adenosyltransferase I/III (MAT I/III) deficiency is characterized by persistent hypermethioninemia. The clinical manifestations in cases with MAT I/III deficiency vary from a complete lack of symptoms to neurological problems associated with brain demyelination. We experienced a neonatal case with MAT I/III deficiency, in which severe hypermethioninemia was detected during the newborn screening test. The patient gradually showed hyperreflexia, foot clonus, and irritability from the age of 1 month onwards, and his brain magnetic resonance imaging scans showed abnormal signal intensity in the bilateral central tegmental tracts...
October 30, 2018: Brain & Development
Y F Zhou, Z Zhou, F Batistel, I Martinez-Cortés, R T Pate, D L Luchini, J J Loor
Insufficient supply of Met and choline (Chol) around parturition could compromise hepatic metabolism and milk protein synthesis in dairy cows. Mechanistic responses associated with supply of Met or Chol in primary liver cells enriched with hepatocytes (PHEP) from cows have not been thoroughly ascertained. Objectives were to isolate and culture PHEP to examine abundance of genes and proteins related to transmethylation, transsulfuration, and cytidine 5'-diphosphocholine (CDP-choline) pathways in response to Met or Chol...
October 10, 2018: Journal of Dairy Science
Hongzheng Sun, Jian Kang, Jianmin Su, Jinjing Zhang, Lei Zhang, Xin Liu, Jingcheng Zhang, Fengyu Wang, Zhenzhen Lu, Xupeng Xing, HuanHuan Chen, Yong Zhang
Methionine adenosyltransferase II (MAT2A) is essential to the synthesis of S-adenosylmethionine, a major methyl donor, from L-methionine and ATP. Upon fertilization, zygotic genome activation (ZGA) marks the period that transforms the genome from transcriptional quiescence to robust transcriptional activity. During this period, embryonic epigenome undergoes extensive modifications, including histone methylation changes. However, whether MAT2A participates in histone methylation at the ZGA stage is unknown. Herein, we identified that MAT2A is a pivotal factor for ZGA in mouse embryos...
September 27, 2018: Biology of Reproduction
Vinod Dagar, Wendy Hutchison, Andrea Muscat, Anita Krishnan, David Hoke, Ashley Buckle, Priscillia Siswara, David J Amor, Jeffrey Mann, Jason Pinner, Alison Colley, Meredith Wilson, Rani Sachdev, George McGillivray, Matthew Edwards, Edwin Kirk, Felicity Collins, Kristi Jones, Juliet Taylor, Ian Hayes, Elizabeth Thompson, Christopher Barnett, Eric Haan, Mary-Louise Freckmann, Anne Turner, Susan White, Ben Kamien, Alan Ma, Fiona Mackenzie, Gareth Baynam, Cathy Kiraly-Borri, Michael Field, Tracey Dudding-Byth, Elizabeth M Algar
BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder with a population frequency of approximately 1 in 10,000. The most common epigenetic defect in BWS is a loss of methylation (LOM) at the 11p15.5 imprinting centre, KCNQ1OT1 TSS-DMR, and affects 50% of cases. We hypothesised that genetic factors linked to folate metabolism may play a role in BWS predisposition via effects on methylation maintenance at KCNQ1OT1 TSS-DMR. RESULTS: Single nucleotide variants (SNVs) in the folate pathway affecting methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), 5-methyltetrahydrofolate-homocysteine S-methyltransferase (MTR), cystathionine beta-synthase (CBS) and methionine adenosyltransferase (MAT1A) were examined in 55 BWS patients with KCNQ1OT1 TSS-DMR LOM and in 100 unaffected cases...
August 30, 2018: Clinical Epigenetics
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
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 [methionine-deficient diet (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...
September 21, 2018: Carcinogenesis
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
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
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...
September 2018: Biochimica et biophysica acta. Molecular basis of disease
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...
September 2018: Molecular Carcinogenesis
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 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 α1 (MATα1) and other transcription factors at the E-box element to repress transcription. We studied mechanisms of MAFG up-regulation in cholestatic tissues and the pathways by which S-adenosylmethionine (SAMe) and ursodeoxycholic acid (UDCA) prevent the increase in MAFG expression...
August 2018: Gastroenterology
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
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
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
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
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
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