Article
Biochemistry & Molecular Biology
Po-Ming Chen, Cheng-Hsueh Tsai, Chieh-Cheng Huang, Hau-Hsuan Hwang, Jian-Rong Li, Chun-Chi Liu, Hsin-An Ko, En-Pei Isabel Chiang
Summary: This study found that the downregulation or defect of MAT1A and GNMT genes can enrich the protein-associated translation process, which may contribute to poor prognosis in hepatocellular carcinoma (HCC).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Claudia De Fusco, Marianne Schimpl, Ulf Borjesson, Tony Cheung, Iain Collie, Laura Evans, Priyanka Narasimhan, Christopher Stubbs, Mercedes Vazquez-Chantada, David J. Wagner, Michael Grondine, Matthew G. Sanders, Sharon Tentarelli, Elizabeth Underwood, Argyrides Argyrou, James M. Smith, James T. Lynch, Elisabetta Chiarparin, Graeme Robb, Sharan K. Bagal, James S. Scott
Summary: MAT2a is an enzyme that synthesizes the essential metabolite SAM, making it an attractive target for treating MTAP-deleted cancers sensitive to its inhibition. Through structure-guided design and systematic SAR exploration, a potent series of MAT2a inhibitors has been developed, demonstrating promising antitumor response in in vivo studies.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zenon Konteatis, Jeremy Travins, Stefan Gross, Katya Marjon, Amelia Barnett, Everton Mandley, Brandon Nicolay, Raj Nagaraja, Yue Chen, Yabo Sun, Zhixiao Liu, Jie Yu, Zhixiong Ye, Fan Jiang, Wentao Wei, Cheng Fang, Yi Gao, Peter Kalev, Marc L. Hyer, Byron DeLaBarre, Lei Jin, Anil K. Padyana, Lenny Dang, Joshua Murtie, Scott A. Biller, Zhihua Sui, Kevin M. Marks
Summary: This study reports the discovery of highly potent, selective MAT2A inhibitors that overcome previous challenges in targeting MAT2A. Through fragment screening and structure-guided design, these inhibitors significantly reduce SAM levels in cancer cells and selectively block proliferation of MTAP-null cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Agnidipta Ghosh, Courtney N. Niland, Sean M. Cahill, Nishant M. Karadkhelkar, Vern L. Schramm
Summary: Human methionine adenosyltransferase MAT2A plays a crucial role in providing S-adenosyl-L-methionine (AdoMet) for methyl-transfer reactions, influencing expression patterns in development and cancer. Studies describe the mechanism of AdoMet and triphosphate formation, as well as the hydrolysis process of triphosphate to pyrophosphate and phosphate by MAT2A. Crystallographic analysis reveals the catalytic site geometry of the transition-state reconstruction, predicting a loose transition state with characteristics of symmetric nucleophilic displacement.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Cell Biology
Fan Tong, Yuchen Zhang, Chi Chen, Ling Zhu, Yijun Lu, Zhanming Zhang, Ting Chen, Jiaxuan Yan, Jing Zheng, Xiaoxu Zhao, Duo Zhou, Xin Yang, Rulai Yang, Xiaohui Cang, Pingping Jiang, Qiang Shu
Summary: Methionine adenosyltransferase deficiency (MATD) is a rare metabolic disorder caused by MAT1A mutations. Our study analyzed a large dataset and found clinical and genetic heterogeneity in MATD patients, with higher severity in autosomal recessive cases. We identified different genotypes and clinical manifestations, and treatment with a methionine-restricted diet and other supplements proved effective. Our findings provide new insights for the diagnosis and management of MATD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Xingping Chen, Junyi Luo, Lekai Yang, Yue Guo, Yaotian Fan, Jie Liu, Jiajie Sun, Yongliang Zhang, Qingyan Jiang, Ting Chen, Qianyun Xi
Summary: The combination of betaine and miR-143 promotes lipolysis and glucose utilization, while repressing lipogenesis and gluconeogenesis, playing crucial roles in metabolic regulation and serving as key regulators and biomarkers for metabolic diseases prevention and diagnosis.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Yaqin Li, Guoxin Hu, Furong Huang, Mingtai Chen, Yihua Chen, Youhua Xu, Guangdong Tong
Summary: This study reveals that the CTBP1/HDAC1/HDAC2 complex-induced MAT1A suppression is linked to immune escape and reduced ferroptosis of HCC cells, providing a potential therapeutic target.
LABORATORY INVESTIGATION
(2023)
Article
Biology
G. Gokul, Jogender Singh
Summary: This study reveals that the redox reagent DTT can induce stress in the endoplasmic reticulum and disrupt protein folding, leading to cellular toxicity. The presence of vitamin B12 in the bacterial diet can alleviate DTT toxicity. Loss of function of the SAM-dependent methyltransferase gene R08E5.3 confers resistance to DTT. Depletion of SAM is identified as the underlying mechanism of DTT toxicity. The unfolded protein response pathway involving IRE-1/XBP-1 is required to counteract DTT toxicity at high concentrations.
Review
Biochemistry & Molecular Biology
Joanna Perla-Kajan, Hieronim Jakubowski
Summary: Dysregulation of one-carbon metabolism is associated with various diseases and plays a crucial role in COVID-19. The metabolism of cells infected by the SARS-CoV-2 virus is altered, affecting vitamin B-12 and glutathione metabolism, which may be related to the symptoms and disease mechanisms of COVID-19.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Silong Zhang, Luolong Qing, Ziwei Wang, Yu Zhang, Yuanyuan Li, Huaxiang Fang, Yi Liu, Huan He
Summary: Inhibition of MAT2A in cancers with MTAP deletion has shown synthetic lethality for precise cancer treatment. A new tetrahydrobenzo[4,5]imidazo-[1,2-a]pyrazine fragment (compound 8) has been discovered to efficiently inhibit MAT2A enzymatic activity and proliferation of MTAP-null cancer cells. Introduction of an amide motif (compound 28) in the core structure significantly enhanced the in vivo potency, leading to tumor regression in a xenograft MTAP-depleted colon tumor model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Mingzhe Ma, Pengfei Kong, Yakai Huang, Jiangli Wang, Xiaocen Liu, YiRen Hu, Xingxing Chen, Chunyan Du, Hui Yang
Summary: This study identified a link between methionine cycle activity and susceptibility to ferroptosis, and discovered the role of MAT2A in ferroptosis resistance.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Cell Biology
Lude Wang, Bin Hu, Kailing Pan, Jie Chang, Xiaoya Zhao, Lin Chen, Haiping Lin, Jing Wang, Gezhi Zhou, Wenxia Xu, Jianlie Yuan
Summary: This study investigated the molecular mechanism of glioma response to methionine restriction, revealing that under methionine restriction, glioma cells showed high expression of MAT2A, and an inhibitor of MAT2A reduced the proliferation of tumor cells. High expression of MAT2A was associated with World Health Organization-grade glioma and increased transfer of its mRNA out of the nucleus.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Linda Lauinger, Peter Kaiser
Summary: The availability of the amino acid methionine plays a crucial role in the physiology of individual cells and whole organisms, particularly in cancer cells and healthy lifespan. Cells need mechanisms to sense methionine availability, and respond through transcriptional and signaling states to maintain metabolic balance and genomic integrity during methionine starvation conditions.
Article
Microbiology
Sheng Yin, Dongmei Yang, Yiying Zhu, Baozhu Huang
Summary: The study reveals that amino acid metabolism can regulate the biosynthesis of Monascus pigments (MPs), and methionine and S-adenosylmethionine (SAM) play different roles in the regulation of MPs biosynthesis in Monascus purpureus RP2. The expression of SAM synthetase leads to an increased expression of transcriptional regulatory proteins of the MPs biosynthesis gene cluster, while the addition of SAM results in increased expression of MPs biosynthesis activators and the global regulator LaeA. These findings provide a new perspective for understanding the regulation of MPs biosynthesis in M. purpureus.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Cell Biology
Takujiro Homma, Sho Kobayashi, Junichi Fujii
Summary: This study found that ferroptosis occurs in the absence of cystine or methionine, leading to lipid peroxidation and cell cycle arrest. Surprisingly, the simultaneous deprivation of both cystine and methionine failed to induce ferroptosis, but supplementation with S-adenosylmethionine restored ferroptosis. The results suggest that elevated lipid peroxidation products during cell cycle progression are involved in ferroptosis execution under conditions of cysteine starvation.
Article
Food Science & Technology
Carlos L. Cespedes, Cristian Balbontin, Jose G. Avila, Mariana Dominguez, Julio Alarcon, Cristian Paz, Viviana Burgos, Leandro Ortiz, Ignacio Penaloza-Castro, David S. Seigler, Isao Kubo
FOOD AND CHEMICAL TOXICOLOGY
(2017)
Article
Food Science & Technology
Carlos L. Cespedes, Natalia Pavon, Mariana Dominguez, Julio Alarcon, Cristian Balbontin, Isao Kubo, Mohammed El-Hafidi, Jose G. Avila
FOOD AND CHEMICAL TOXICOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Jesus Rafael Rodriguez-Aguilera, Carlos Guerrero-Hernandez, Rosario Perez-Molina, Carla Elizabeth Cadena-del-Castillo, Rebeca Perez-Cabeza de Vaca, Nuria Guerrero-Celis, Mariana Dominguez-Lopez, Adrian Rafael Murillo-de-Ozores, Rodrigo Arzate-Mejia, Felix Recillas-Targa, Victoria Chagoya de Sanchez
JOURNAL OF CELLULAR BIOCHEMISTRY
(2018)
Article
Pharmacology & Pharmacy
Enrique Chavez, Maria Guadalupe Lozano-Rosas, Mariana Dominguez-Lopez, Gabriela Velasco-Loyden, Jesus Rafael Rodriguez-Aguilera, Concepcion Jose-Nunez, Marietta Tuena de Gomez-Puyou, Victoria Chagoya de Sanchez
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2017)
Article
Biochemistry & Molecular Biology
Mayte Cossio-Ayala, Mariana Dominguez-Lopez, Erika Mendez-Enriquez, Maria del Carmen Portillo-Tellez, Enrique Garcia-Hernandez
Article
Immunology
Rebeca Perez-Cabeza de Vaca, Mariana Dominguez-Lopez, Nuria Guerrero-Celis, Jesus R. Rodriguez-Aguilera, Victoria Chagoya de Sanchez
INTERNATIONAL IMMUNOPHARMACOLOGY
(2018)
Article
Chemistry, Physical
Hilda Cornejo-Garrido, Antonio Nieto-Camacho, Virginia Gomez-Vidales, Maria Teresa Ramirez-Apan, Paz del Angel, Jose Ascencion Montoya, Mariana Dominguez-Lopez, Dania Kibanova, Javiera Cervini-Silva
APPLIED CLAY SCIENCE
(2012)
Article
Plant Sciences
Mariana Dominguez, Jose G. Avila, Antonio Nieto, Carlos L. Cespedes
PHARMACEUTICAL BIOLOGY
(2011)
Article
Multidisciplinary Sciences
Jesus Rafael Rodriguez-Aguilera, Szilvia Ecsedi, Chloe Goldsmith, Marie-Pierre Cros, Mariana Dominguez-Lopez, Nuria Guerrero-Celis, Rebeca Perez-Cabeza de Vaca, Isabelle Chemin, Felix Recillas-Targa, Victoria Chagoya de Sanchez, Hector Hernandez-Vargas
SCIENTIFIC REPORTS
(2020)
Article
Integrative & Complementary Medicine
J. Rodrigo Salazar, Patricio Torres, Blanca Serrato, Mariana Dominguez, Julio Alarcon, Carlos L. Cespedes
BOLETIN LATINOAMERICANO Y DEL CARIBE DE PLANTAS MEDICINALES Y AROMATICAS
(2015)
Article
Integrative & Complementary Medicine
Mariana Dominguez, Anna S. Keck, Elizabeth H. Jeffery, Carlos L. Cespedes
BOLETIN LATINOAMERICANO Y DEL CARIBE DE PLANTAS MEDICINALES Y AROMATICAS
(2010)
Article
Biochemistry & Molecular Biology
Mariana Dominguez, J. Camilo Marin, Baldomero Esquivel, Carlos L. Cespedes
Article
Agriculture, Multidisciplinary
M Dominguez, A Nieto, JC Marin, AS Keck, E Jeffery, CL Céspedes
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2005)