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JOURNAL ARTICLE
Alba Capelo-Diz, Sofía Lachiondo-Ortega, David Fernández-Ramos, Jorge Cañas-Martín, Naroa Goikoetxea-Usandizaga, Marina Serrano-Maciá, Maria J González-Rellan, Laura Mosca, Joan Blazquez-Vicens, Alberto Tinahones-Ruano, Marcos F Fondevila, Mason Buyan, Teresa C Delgado, Virginia Gutierrez de Juan, Paula Ayuso-García, Alejandro Sánchez-Rueda, Sergio Velasco-Avilés, Héctor Fernández-Susavila, Cristina Riobello-Suárez, Bartlomiej Dziechciarz, Cristina Montiel-Duarte, Fernando Lopitz-Otsoa, Maider Bizkarguenaga, Jon Bilbao-García, Ganeko Bernardo-Seisdedos, Ana Senra, Mario Soriano-Navarro, Oscar Millet, Ángel Díaz-Lagares, Ana B Crujeiras, Aida Bao-Caamano, Diana Cabrera, Sebastiaan van Liempd, Miguel Tamayo-Carro, Luigi Borzacchiello, Beatriz Gomez-Santos, Xabier Buqué, Diego Sáenz de Urturi, Francisco González-Romero, Jorge Simon, Rubén Rodríguez-Agudo, Asier Ruiz, Carlos Matute, Daniel Beiroa, Juan M Falcon-Perez, Patricia Aspichueta, Juan Rodríguez-Cuesta, Marina Porcelli, María A Pajares, Cristina Ameneiro, Miguel Fidalgo, Ana M Aransay, Tomas Lama-Díaz, Miguel G Blanco, Miguel López, Ricardo Villa-Bellosta, Timo D Müller, Rubén Nogueiras, Ashwin Woodhoo, María Luz Martínez-Chantar, Marta Varela-Rey
There has been an intense focus to uncover the molecular mechanisms by which fasting triggers the adaptive cellular responses in the major organs of the body. Here, we show that in mice, hepatic S-adenosylmethionine (SAMe)-the principal methyl donor-acts as a metabolic sensor of nutrition to fine-tune the catabolic-fasting response by modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, β-oxidation, and ATP production in the liver, together with FGF21-mediated lipolysis and thermogenesis in adipose tissues...
August 8, 2023: Cell Metabolism
#22
JOURNAL ARTICLE
Vitor Teixeira, Ibrahim Mohamed, Jean-Claude Lavoie
In premature infants receiving parenteral nutrition, oxidative stress is a trigger for the development of bronchopulmonary dysplasia, which is an important factor in the development of adult lung diseases. Neonatal vitamin C and glutathione deficiency is suspected to induce permanent modification of redox metabolism favoring the development of neonatal and adult lung diseases. A total of 64 3-day-old guinea pigs were fed an oral diet that was either complete or deficient in vitamin C (VCD), cysteine (CD) (glutathione-limiting substrate) or both (DD) for 4 days...
June 29, 2023: Antioxidants (Basel, Switzerland)
#23
JOURNAL ARTICLE
Ashlie Santaliz-Casiano, Dhruv Mehta, Oana C Danciu, Hariyali Patel, Landan Banks, Ayesha Zaidi, Jermya Buckley, Garth H Rauscher, Lauren Schulte, Lauren Ro Weller, Deanna Taiym, Elona Liko-Hazizi, Natalie Pulliam, Sarah M Friedewald, Seema Khan, J Julie Kim, William Gradishar, Scott Hegerty, Jonna Frasor, Kent F Hoskins, Zeynep Madak-Erdogan
African American (AA) women in the United States have a 40% higher breast cancer mortality rate than Non-Hispanic White (NHW) women. The survival disparity is particularly striking among (estrogen receptor positive) ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic pathways typically activated in patients with ER+ breast cancer. We collected pretreatment plasma from AA and NHW ER+ breast cancer cases (AA n = 48, NHW n = 54) and cancer-free controls (AA n = 100, NHW n = 48) to conduct an untargeted metabolomics analysis using gas chromatography mass spectrometry (GC-MS) to identify metabolites that may be altered in the different racial groups...
July 26, 2023: Scientific Reports
#24
JOURNAL ARTICLE
Wenping Ding, Minqi Zhou, Huayu Li, Miao Li, Yanping Qiu, Yu Yin, Lifeng Pan, Wenchao Yang, Yanan Du, Xingang Zhang, Zhijun Tang, Wen Liu
Modification of organic molecules with fluorine functionalities offers a critical approach to develop new pharmaceuticals. Here, we report a multienzyme strategy for biocatalytic fluoroalkylation using S -adenosyl-l-methionine (SAM)-dependent methyltransferases (MTs) and fluorinated SAM cofactors prepared from ATP and fluorinated l-methionine analogues by an engineered human methionine adenosyltransferase hMAT2AI322A . This work introduces the first example of biocatalytic 3,3-difluoroallylation. Importantly, this strategy can be applied to late-stage site-selective fluoroalkylation of complex molecule vancomycin with conversions up to 99%...
July 25, 2023: Organic Letters
#25
JOURNAL ARTICLE
Zhenyin Chen, Wei Chen, Zhayila Reheman, Haodong Jiang, Jiahui Wu, Xing Li
Sensors to measure the abundance and signaling of intracellular molecules are crucial for understanding their physiological functions. Although conventional fluorescent protein-based sensors have been designed, RNA-based sensors are promising imaging tools. Numerous RNA-based sensors have been developed. These sensors typically contain RNA G-quadruplex (RG4) motifs and thus may be suboptimal in living cells. Here we describe RNA-based sensors based on Pepper, a fluorogenic RNA without an RG4 motif. With Pepper, we engineered various sensors for metabolites, synthetic compounds, proteins and metal ions in vitro and in living cells...
July 24, 2023: Nucleic Acids Research
#26
JOURNAL ARTICLE
Yanmeng Wang, Catharina Muylaert, Arne Wyns, Philip Vlummens, Kim De Veirman, Karin Vanderkerken, Esther Zaal, Celia Berkers, Jérome Moreaux, Elke De Bruyne, Eline Menu
Multiple Myeloma (MM) is the second most prevalent hematological malignancy and is incurable due to the inevitable development of drug resistance. The methionine adenosyltransferase 2α (MAT2A) is the primary producer of the methyl donor S-adenosylmethionine (SAM) and several studies reported MAT2A deregulation in different solid cancers. As the role of MAT2A in MM is not studied yet, the aim of this study was to clarify the potential role and underlying molecular mechanisms of MAT2A in MM, exploring new therapeutic options to overcome drug resistance...
July 20, 2023: Haematologica
#27
JOURNAL ARTICLE
Shuchi Xia, Yun Liang, Yuqing Shen, Wuxue Zhong, Yiqun Ma
Osteosarcoma (OS) is the most frequent primary malignant bone tumor. Ferroptosis, a form of regulated cell death, is a key tumor suppression mechanism. Although methionine adenosyltransferase II alpha (MAT2A) has been reported to inhibit several tumor cells, it is unclear whether inhibition of MAT2A in OS cells can reduce ferroptosis. CCK-8, flow cytometry, and Transwell assays were performed to evaluate cell viability, cell apoptosis/cycle, and cell migration, respectively. The levels of ferrous iron and glutathione (GSH) levels in cells were measured to evaluate the degree of cell ferroptosis...
August 2023: Journal of Bone Oncology
#28
JOURNAL ARTICLE
Vincenzo Lopreiato, Abdulrahman S Alharthi, Yusheng Liang, Ahmed A Elolimy, Ryan Bucktrout, Mike T Socha, Erminio Trevisi, Juan J Loor
Vitamin B12 plays a role in the remethylation of homocysteine to Met, which then serves as a substrate for Met adenosyltransferase (MAT) to synthesize S-adenosylmethionine (SAM). We investigated effects of feeding two cobalt sources [Co-glucoheptonate (CoPro) or CoPectin, Zinpro Corp.], an experimental ruminally-available source of folic acid (FOA), and rumen-protected Met (RPM) on performance and hepatic one-carbon metabolism in peripartal Holstein cows. From -30 to 30 d around calving, 72 multiparous cows were randomly allocated to: CoPro, CoPro + FOA, CoPectin + FOA, or CoPectin + FOA + RPM...
June 25, 2023: Animals: An Open Access Journal From MDPI
#29
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
August 24, 2023: Neuroreport
#30
JOURNAL ARTICLE
Yaqin Li, Guoxin Hu, Furong Huang, Mingtai Chen, Yihua Chen, Youhua Xu, Guangdong Tong
Hepatocellular carcinoma (HCC) remains a significant health burden globally due to its high prevalence and morbidity. C-terminal binding protein 1 (CTBP1) is a transcriptional co-repressor that modulates gene transcription by interacting with transcription factors or chromatin-modifying enzymes. High CTBP1 expression has been associated with the progression of various human cancers. In this study, Bioinformatics analysis suggests the existence of a CTBP1/histone deacetylase 1 (HDAC1)/HDAC2 transcriptional complex that regulates the expression of methionine adenosyltransferase 1A (MAT1A), whose loss has been associated with ferroptosis suppression and HCC development...
May 23, 2023: Laboratory Investigation; a Journal of Technical Methods and Pathology
#31
JOURNAL ARTICLE
Arne Hoffmann, Kai H Schülke, Stephan C Hammer, Andrea Rentmeister, Nicolas V Cornelissen
Methyltransferases provide excellent specificity in late-stage alkylation of biomolecules. Their dependence on S -adenosyl-L-methionine (SAM) mandates efficient access to SAM analogues for biocatalytic applications. We directly compared halide methyltransferase (HMT) and methionine adenosyltransferase (MAT) to access SAM analogues and explored their utility in cascade reactions with NovO for regioselective, late-stage Friedel-Crafts alkylation of a coumarin. The HMT cascade efficiently provided SAM for methylation, while the MAT cascade also supplied high levels of SAM analogues for alkylation reactions...
April 18, 2023: Chemical Communications: Chem Comm
#32
Sarita Garg, Lauren C Morehead, Jordan T Bird, Stefan Graw, Allen Gies, Aaron J Storey, Alan J Tackett, Rick D Edmondson, Samuel G Mackintosh, Stephanie D Byrum, Isabelle R Miousse
Dietary methionine restriction is associated with a reduction in tumor growth in preclinical studies and an increase in lifespan in animal models. The mechanism by which methionine restriction inhibits tumor growth while sparing normal cells is incompletely understood. We do know that normal cells can utilize methionine or homocysteine interchangeably (methionine independence) while most cancer cells are strictly dependent on methionine availability. Here, we compared a typical methionine dependent and a rare methionine independent melanoma cell line...
April 5, 2023: bioRxiv
#33
JOURNAL ARTICLE
Christina H Acosta, Garrett A Clemons, Cristiane T Citadin, William C Carr, Mariana Sayuri Berto Udo, Vesna Tesic, Henry W Sanicola, Anne H Freelin, Jamie B Toms, J Dedrick Jordan, Bharat Guthikonda, Celeste Yin-Chieh Wu, Reggie Hui-Chao Lee, Hung Wen Lin
Mild traumatic brain injury affects the largest proportion of individuals in the United States and world-wide. Pre-clinical studies of repetitive and mild traumatic brain injury (rmTBI) have been limited in their ability to recapitulate human pathology (i.e. diffuse rotational injury). We used the closed-head impact model of engineered rotation acceleration (CHIMERA) to simulate rotational injury observed in patients and to study the pathological outcomes post-rmTBI using C57BL/6J mice. Enhanced cytokine production was observed in both the cortex and hippocampus to suggest neuroinflammation...
April 6, 2023: Neurochemistry International
#34
JOURNAL ARTICLE
Silong Zhang, Luolong Qing, Ziwei Wang, Yu Zhang, Yuanyuan Li, Huaxiang Fang, Yi Liu, Huan He
Inhibition of methionine adenosyltransferase 2A (MAT2A) in cancers with a deletion of methylthioadenosine phosphorylase (MTAP) gene leads to synthetic lethality, thus receiving significant interest in the field of precise cancer treatment. Herein, we report the discovery of a tetrahydrobenzo[4,5]imidazo[1,2- a ]pyrazine fragment which occupies the MAT2A allosteric pocket. The lead compound 8 exhibited extremely high potency to inhibit MAT2A enzymatic activity (IC50 = 18 nM) and proliferation of MTAP-null cancer cells (IC50 = 52 nM)...
April 13, 2023: Journal of Medicinal Chemistry
#35
JOURNAL ARTICLE
Krista van Blokland-Post, Maarten F Weber, Monique E van Wolferen, Louis C Penning, Freek J van Sluijs, Anne Kummeling
BACKGROUND: In dogs with a congenital extrahepatic portosystemic shunt (EHPSS), outcome after surgical attenuation is difficult to predict. OBJECTIVES: Develop a minimally invasive test to predict outcome after surgical EHPSS attenuation and establish risk factors for postattenuation seizures (PAS). ANIMALS: Eighty-five client-owned dogs referred for surgical attenuation of a single EHPSS. METHODS: mRNA expression of 8 genes was measured in preoperatively collected venous blood samples...
March 19, 2023: Journal of Veterinary Internal Medicine
#36
JOURNAL ARTICLE
Mu Feng, Hilda Namanja-Magliano, Saranathan Rajagopalan, Tanmay Mishra, Rodrigo G Ducati, Brett M Hirsch, Libusha Kelly, Wendy Szymczak, Jorge Eduardo Fajardo, Simone Sidoli, Andras Fiser, William R Jacobs, Vern L Schramm
Helicobacter pylori is found in the gut lining of more than half of the world's population, causes gastric ulcers, and contributes to stomach cancers. Menaquinone synthesis in H. pylori relies on the rare futalosine pathway, where H. pylori 5'-methylthioadenosine nucleosidase (MTAN) is proposed to play an essential role. Transition state analogues of MTAN, including BuT-DADMe-ImmA (BTDIA) and MeT-DADMe-ImmA (MTDIA), exhibit bacteriostatic action against numerous diverse clinical isolates of H. pylori with minimum inhibitory concentrations (MIC's) of <2 ng/mL...
March 15, 2023: ACS Infectious Diseases
#37
JOURNAL ARTICLE
Nika Rajabian, Izuagie Ikhapoh, Shahryar Shahini, Debanik Choudhury, Ramkumar Thiyagarajan, Aref Shahini, Joseph Kulczyk, Kendall Breed, Shilpashree Saha, Mohamed Alaa Mohamed, Susan B Udin, Aimee Stablewski, Kenneth Seldeen, Bruce R Troen, Kirkwood Personius, Stelios T Andreadis
We investigate the age-related metabolic changes that occur in aged and rejuvenated myoblasts using in vitro and in vivo models of aging. Metabolic and signaling experiments reveal that human senescent myoblasts and myoblasts from a mouse model of premature aging suffer from impaired glycolysis, insulin resistance, and generate Adenosine triphosphate by catabolizing methionine via a methionine adenosyl-transferase 2A-dependant mechanism, producing significant levels of ammonium that may further contribute to cellular senescence...
February 16, 2023: Nature Communications
#38
JOURNAL ARTICLE
Structure of the Caenorhabditis elegans m6A methyltransferase METT10 that regulates SAM homeostasis.
Jue Ju, Tomohiko Aoyama, Yuka Yashiro, Seisuke Yamashita, Hidehito Kuroyanagi, Kozo Tomita
In Caenorhabditis elegans, the N6-methyladenosine (m6A) modification by METT10, at the 3'-splice sites in S-adenosyl-l-methionine (SAM) synthetase (sams) precursor mRNA (pre-mRNA), inhibits sams pre-mRNA splicing, promotes alternative splicing coupled with nonsense-mediated decay of the pre-mRNAs, and thereby maintains the cellular SAM level. Here, we present structural and functional analyses of C. elegans METT10. The structure of the N-terminal methyltransferase domain of METT10 is homologous to that of human METTL16, which installs the m6A modification in the 3'-UTR hairpins of methionine adenosyltransferase (MAT2A) pre-mRNA and regulates the MAT2A pre-mRNA splicing/stability and SAM homeostasis...
February 16, 2023: Nucleic Acids Research
#39
JOURNAL ARTICLE
Aaron E Robinson, Aleksandra Binek, Komal Ramani, Niveda Sundararaman, Lucía Barbier-Torres, Ben Murray, Vidya Venkatraman, Simion Kreimer, Angela Mc Ardle, Mazen Noureddin, David Fernández-Ramos, Fernando Lopitz-Otsoa, Virginia Gutiérrez de Juan, Oscar Millet, José M Mato, Shelly C Lu, Jennifer E Van Eyk
Methionine adenosyltransferase 1a (MAT1A) is responsible for hepatic S-adenosyl-L-methionine (SAMe) biosynthesis. Mat1a -/- mice have hepatic SAMe depletion, develop nonalcoholic steatohepatitis (NASH) which is reversed with SAMe administration. We examined temporal alterations in the proteome/phosphoproteome in pre-disease and NASH Mat1a -/- mice, effects of SAMe administration, and compared to human nonalcoholic fatty liver disease (NAFLD). Mitochondrial and peroxisomal lipid metabolism proteins were altered in pre-disease mice and persisted in NASH Mat1a -/- mice, which exhibited more progressive alterations in cytoplasmic ribosomes, ER, and nuclear proteins...
February 17, 2023: IScience
#40
JOURNAL ARTICLE
Chenqi Cao, Kaili Nie, Haijun Xu, Luo Liu
S-adenosyl-L-methionine (SAM) is the active form of methionine, which participates in various metabolic reactions and plays a vital role. It is mainly used as a precursor by three key metabolic pathways: trans-methylation, trans-sulfuration, and trans-aminopropylation. Methionine adenosyltransferase (MAT) is the only enzyme to produce SAM from methionine and ATP. However, there is no efficient and accurate method for high-throughput detection of SAM, which is the major obstacles of directed evolution campaigns for MAT...
January 18, 2023: Applied Biochemistry and Biotechnology
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