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https://www.readbyqxmd.com/read/29460630/insights-on-the-origin-of-catalysis-on-glycine-n-methyltransferase-from-computational-modelling
#1
Katarzyna Świderek, Iñaki Tuñón, Ian H Williams, Vicent Moliner
The origin of enzyme catalysis remains a question of debate despite much intense study. We report a QM/MM theoretical study of the SN2 methyl transfer reaction catalyzed by a glycine N-methyltransferase (GNMT) and three mutants to test whether recent experimental observations of rate-constant reductions and variations in inverse secondary α-3H kinetic isotope effects (KIEs) should be attributed to changes in the methyl donor-acceptor distance (DAD): is catalysis due to a compression effect? Semiempirical (AM1) and DFT (M06-2X) methods were used to describe the QM subset of atoms, while OPLS-AA and TIP3P classical force fields were used for the protein and water molecules, respectively...
February 20, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29416063/ahr-and-shp-regulate-phosphatidylcholine-and-s-adenosylmethionine-levels-in-the-one-carbon-cycle
#2
Young-Chae Kim, Sunmi Seok, Sangwon Byun, Bo Kong, Yang Zhang, Grace Guo, Wen Xie, Jian Ma, Byron Kemper, Jongsook Kim Kemper
Phosphatidylcholines (PC) and S-adenosylmethionine (SAM) are critical determinants of hepatic lipid levels, but how their levels are regulated is unclear. Here, we show that Pemt and Gnmt, key one-carbon cycle genes regulating PC/SAM levels, are downregulated after feeding, leading to decreased PC and increased SAM levels, but these effects are blunted in small heterodimer partner (SHP)-null or FGF15-null mice. Further, aryl hydrocarbon receptor (AhR) is translocated into the nucleus by insulin/PKB signaling in the early fed state and induces Pemt and Gnmt expression...
February 7, 2018: Nature Communications
https://www.readbyqxmd.com/read/29375826/dietary-betaine-activates-hepatic-vtgii-expression-in-laying-hens-associated-with-hypomethylation-of-gr-gene-promoter-and-enhanced-gr-expression
#3
Nagmeldin A Omer, Yun Hu, Yan Hu, Abdulrahman A Idriss, Halima Abobaker, Zhen Hou, Haibo Dong, Ruqian Zhao
Background: Vitellogenin (VTG) is a precursor of egg yolk proteins synthesized within the liver of oviparous vertebrates. Betaine is an important methyl donor that is reported to improve egg production of laying hens with an unclear mechanism. In the present study, we fed betaine-supplemented diet (0.5%) to laying hens for 4 wk and investigated its effect on VTGII expression in the liver. Results: Betaine did not affect chicken weight, but significantly (P < 0...
2018: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29288362/identification-of-genes-highly-downregulated-in-pancreatic-cancer-through-a-meta-analysis-of-microarray-datasets-implications-for-discovery-of-novel-tumor-suppressor-genes-and-therapeutic-targets
#4
Nalin C W Goonesekere, Wyatt Andersen, Alex Smith, Xiaosheng Wang
PURPOSE: The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a 5-year survival rate of about 7%. Recent failures of targeted therapies inhibiting kinase activity in clinical trials have highlighted the need for new approaches towards combating this deadly disease. METHODS: In this study, we have identified genes that are significantly downregulated in PC, through a meta-analysis of large number of microarray datasets...
December 29, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29122967/hepatic-accumulation-of-s-adenosylmethionine-in-hamsters-with-non-alcoholic-fatty-liver-disease-associated-to-metabolic-syndrome-under-selenium-and-vitamin-e-deficiency
#5
Josep M Del Bas, Benjamín Rodríguez, Francesc Puiggròs, Silvia Mariné, Miguel Angel Rodríguez, David Moriña, Lluís Armengol, Antoni Caimari, Lluís Arola
Progression of non-alcoholic fatty liver disease (NAFLD) in the context of metabolic syndrome (MetS) is only partially explored due to the lack of preclinical models. In order to study the alterations in hepatic metabolism that accompany this condition, we developed a model of MetS accompanied by the onset of steatohepatitis (NASH) by challenging golden hamsters with a high fat diet low in vitamin E and selenium (HFD), since combined deficiency results in hepatic necroinflammation in rodents. Metabolomics and transcriptomics integrated analyses of livers revealed an unexpected accumulation of hepatic S-Adenosylmethionine (SAM) when compared with healthy livers likely due to diminished methylation reactions and repression of GNMT...
November 9, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28807745/acute-toxicity-of-functionalized-single-wall-carbon-nanotubes-a-biochemical-histopathologic-and-proteomics-approach
#6
Homa Ahmadi, Mohammad Ramezani, Rezvan Yazdian-Robati, Behzad Behnam, Kamal Razavi Azarkhiavi, Azadeh Hashem Nia, Ahad Mokhtarzadeh, Maryam Matbou Riahi, Bibi Marjan Razavi, Khalil Abnous
Recently carbon nanotubes (CNTs) showed promising potentials in different biomedical applications but their safe use in humans and probable toxicities are still challenging. The aim of this study was to determine the acute toxicity of functionalized single walled carbon nanotubes (SWCNTs). In this project, PEGylated and Tween functionalized SWCNTs were prepared. BALB/c mice were randomly divided into nine groups, including PEGylated SWCNTs (75,150μg/mouse) and PEG, Tween80 suspended SWCNTs, Tween 80 and a control group (intact mice)...
September 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28776913/dietary-methionine-source-and-level-affect-hepatic-sulfur-amino-acid-metabolism-of-broiler-breeder-hens
#7
Jianmei Wan, Xuemei Ding, Jianping Wang, Shiping Bai, Huanwei Peng, Yuheng Luo, Zhuowei Su, Yue Xuan, Keying Zhang
A study was carried out to investigate the effects of dietary methionine source and level on plasma free amino acids patterns and the expression of genes involved in hepatic methionine metabolism in broiler breeders. A total of 2184 broiler breeders were assigned to 13 dietary treatments, with eight replicates per treatment. The 13 treatments included one control group and 12 additional treatments employing two sources and six levels (0.05, 0.10, 0.15, 0.20, 0.25 and 1.00%). Higher plasma methionine concentration was measured for DL-methionine (DLM) treated hens...
August 4, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/28412251/c-myc-antagonises-the-transcriptional-activity-of-the-androgen-receptor-in-prostate-cancer-affecting-key-gene-networks
#8
Stefan J Barfeld, Alfonso Urbanucci, Harri M Itkonen, Ladan Fazli, Jessica L Hicks, Bernd Thiede, Paul S Rennie, Srinivasan Yegnasubramanian, Angelo M DeMarzo, Ian G Mills
Prostate cancer (PCa) is the most common non-cutaneous cancer in men. The androgen receptor (AR), a ligand-activated transcription factor, constitutes the main drug target for advanced cases of the disease. However, a variety of other transcription factors and signaling networks have been shown to be altered in patients and to influence AR activity. Amongst these, the oncogenic transcription factor c-Myc has been studied extensively in multiple malignancies and elevated protein levels of c-Myc are commonly observed in PCa...
April 2017: EBioMedicine
https://www.readbyqxmd.com/read/28264803/maternal-and-infant-genetic-variants-maternal-periconceptional-use-of-selective-serotonin-reuptake-inhibitors-and-risk-of-congenital-heart-defects-in-offspring-population-based-study
#9
Wendy N Nembhard, Xinyu Tang, Zhuopei Hu, Stewart MacLeod, Zachary Stowe, Daniel Webber
Objective To evaluate whether the association between maternal periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and increased risk of congenital heart defects in offspring is modified by maternal or infant genetic variants in folate, homocysteine, or transsulfuration pathways.Design Population based study. DNA from mothers, fathers, and infants was genotyped with an Illumina GoldenGate custom single nucleotide polymorphism panel. A hybrid design based on a log linear model was used to calculate relative risks and Bayesian false discovery probabilities (BFDP) to identify polymorphisms associated with congenital heart defects modified by SSRI use...
March 6, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28205209/characterization-of-the-gnmt-hecth9-prex2-tripartite-relationship-in-the-pathogenesis-of-hepatocellular-carcinoma
#10
Chung-Hsien Li, Chia-Hung Yen, Yen-Fu Chen, Kuo-Jui Lee, Cheng-Chieh Fang, Xian Zhang, Chih-Chung Lai, Shiu-Feng Huang, Hui-Kuan Lin, Yi-Ming Arthur Chen
The pathogenesis of hepatocellular carcinoma (HCC) involves many molecular pathways. Glycine N-methyltransferase (GNMT) is downregulated in almost all HCC and its gene knockout mice developed HCC with high penetrance. We identified PREX2, a novel PTEN inhibitor, as a GNMT-interacting protein. Such interaction enhanced degradation of PREX2 through an E3 ligase HectH9-mediated proteasomal ubiquitination pathway. Depletion of GNMT or HectH9 resulted in AKT activation in a PREX2 dependent manner and enhanced cell proliferation...
May 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28187310/proteomic-analysis-of-liver-tissue-from-rainbow-trout-oncorhynchus-mykiss-under-high-rearing-density-after-administration-of-dietary-vitamin-e-and-selenium-nanoparticles
#11
Mahdi Naderi, Saeed Keyvanshokooh, Amir Parviz Salati, Alireza Ghaedi
The aim of the present study was to investigate the effects of dietary vitamin E (vit E) and selenium nanoparticles (nanoSe) on liver proteome profile of rainbow trout under high density condition. To correlate the proteome modifications with physiological aspects, growth, serum metabolites (cortisol, glucose, lactate, ALT, AST, and ALP), and liver antioxidant-related parameters (SOD, GPx, CAT, and MDA) were also examined. A total of 1275 fish (average weight of 42.6±2.3g) were stocked into 12 tanks at a density of 80kgm(-3)...
June 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/27975938/development-of-chemopreventive-agents-for-hepatocellular-carcinoma-from-excoecaria-formosana-by-a-glycine-n-methyltransferase-gnmt-gene-expression-oriented-screen-platform
#12
H C Wu, C H Yen, Y M Chen, Y H Chang, H S Chang
No abstract text is available yet for this article.
December 2016: Planta Medica
https://www.readbyqxmd.com/read/27739310/-glycine-n-methyltransferase-and-malignant-diseases-of-the-prostate
#13
Z Heger, T Eckschlager, M Stiborová, V Adam
BACKGROUND: Prostate cancer (PC) constitutes a heterogeneous group of diseases with high prevalence rates that are still increasing, particularly in western countries. Since 1980, prostate specific antigen (PSA) and other diagnostic approaches have been used for PC screening; however, some of these approaches are often deemed painful and cause invasive damage of tissue. Therefore, molecular approaches to PC diagnosis are attracting increasing attention, potentially providing patients with less stressful situations and providing better diagnoses and even prognostic information...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27716281/glycine-n-methyltransferase-deficiency-in-female-mice-impairs-insulin-signaling-and-promotes-gluconeogenesis-by-modulating-the-pi3k-akt-pathway-in-the-liver
#14
Yi-Jen Liao, Tzong-Shyuan Lee, Yuh-Ching Twu, Shih-Ming Hsu, Ching-Ping Yang, Chung-Kwe Wang, Yu-Chih Liang, Yi-Ming Arthur Chen
BACKGROUND: Glycine N-methyltransferase (GNMT) is abundantly expressed in the normal liver but is down-regulated in liver cancer tissues. GNMT knockout (Gnmt-/-) mice can spontaneously develop chronic hepatitis, fatty liver, and liver cancer. We previously demonstrated that hepatic GNMT is decreased in high-fat-diet-induced type 2 diabetes mellitus, but its contribution to metabolic syndrome is unclear. Here we show that GNMT modulates key aspects of metabolic syndrome in mice. METHODS: Eleven-week-old Gnmt-/- and wild-type (WT) mice with a C57BL/6 genetic background were used in this study...
October 4, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27648945/downregulation-of-mir-150-expression-by-dna-hypermethylation-is-associated-with-high-2-hydroxy-4-methylthio-butanoic-acid-induced-hepatic-cholesterol-accumulation-in-nursery-piglets
#15
Yimin Jia, Mingfa Ling, Luchu Zhang, Shuxia Jiang, Yusheng Sha, Ruqian Zhao
Excess 2-hydroxy-(4-methylthio)butanoic acid (HMB) supplementation induces hyperhomocysteinemia, which contributes to hepatic cholesterol accumulation. However, it is unclear whether and how high levels of HMB break hepatic cholesterol homeostasis in nursery piglets. In this study, HMB oversupplementation suppressed food intake and decreased body weight in nursery piglets. Hyperhomocysteinemia and higher hepatic cholesterol accumulation were observed in HMB groups. Accordingly, HMB significantly increased the protein content of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and glycine N-methyltransferase (GNMT) but decreased that of acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1)...
October 12, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27526323/modulation-of-long-noncoding-rnas-by-risk-snps-underlying-genetic-predispositions-to-prostate-cancer
#16
Haiyang Guo, Musaddeque Ahmed, Fan Zhang, Cindy Q Yao, SiDe Li, Yi Liang, Junjie Hua, Fraser Soares, Yifei Sun, Jens Langstein, Yuchen Li, Christine Poon, Swneke D Bailey, Kinjal Desai, Teng Fei, Qiyuan Li, Dorota H Sendorek, Michael Fraser, John R Prensner, Trevor J Pugh, Mark Pomerantz, Robert G Bristow, Mathieu Lupien, Felix Y Feng, Paul C Boutros, Matthew L Freedman, Martin J Walsh, Housheng Hansen He
Long noncoding RNAs (lncRNAs) represent an attractive class of candidates to mediate cancer risk. Through integrative analysis of the lncRNA transcriptome with genomic data and SNP data from prostate cancer genome-wide association studies (GWAS), we identified 45 candidate lncRNAs associated with risk to prostate cancer. We further evaluated the mechanism underlying the top hit, PCAT1, and found that a risk-associated variant at rs7463708 increases binding of ONECUT2, a novel androgen receptor (AR)-interacting transcription factor, at a distal enhancer that loops to the PCAT1 promoter, resulting in upregulation of PCAT1 upon prolonged androgen treatment...
October 2016: Nature Genetics
https://www.readbyqxmd.com/read/27355841/convergent-mechanistic-features-between-the-structurally-diverse-n-and-o-methyltransferases-glycine-n-methyltransferase-and-catechol-o-methyltransferase
#17
Jianyu Zhang, Judith P Klinman
Although an enormous and still growing number of biologically diverse methyltransferases have been reported and identified, a comprehensive understanding of the enzymatic methyl transfer mechanism is still lacking. Glycine N-methyltransferase (GNMT), a member of the family that acts on small metabolites as the substrate, catalyzes methyl transfer from S-adenosyl-l-methionine (AdoMet) to glycine to form S-adenosyl-l-homocysteine and sarcosine. We report primary carbon ((12)C/(14)C) and secondary ((1)H3/(3)H3) kinetic isotope effects at the transferred methyl group, together with (1)H3/(3)H3 binding isotope effects for wild-type GNMT and a series of Tyr21 mutants...
July 27, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27198213/possible-selection-of-host-folate-pathway-gene-polymorphisms-in-patients-with-malaria-from-a-malaria-endemic-region-in-north-east-india
#18
Darshana Mirgal, Kanjaksha Ghosh, Jagadish Mahanta, Prafulla Dutta, Shrimati Shetty
BACKGROUND: Recent studies in experimental mice have shown that mild deficiency of methylenetetrahydrofolate reductase (MTHFR) enzyme confers protection against malaria, thus providing an important basis for the hypothesis that MTHFR polymorphism, i.e. C677T, might have been subjected to selection pressure against malaria. The present study was undertaken in a malaria endemic region in North East India to assess whether a similar selection advantage exists for other genes in folate metabolism pathway...
May 2016: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27153064/identification-of-1-2-3-4-6-penta-o-galloyl-%C3%AE-d-glucopyranoside-as-a-glycine-n-methyltransferase-enhancer-by-high-throughput-screening-of-natural-products-inhibits-hepatocellular-carcinoma
#19
Rajni Kant, Chia-Hung Yen, Chung-Kuang Lu, Ying-Chi Lin, Jih-Heng Li, Yi-Ming Arthur Chen
Glycine N-methyltransferase (GNMT) expression is vastly downregulated in hepatocellular carcinomas (HCC). High rates of GNMT knockout mice developed HCC, while overexpression of GNMT prevented aflatoxin-induced carcinogenicity and inhibited liver cancer cell proliferation. Therefore, in this study, we aimed for the identification of a GNMT inducer for HCC therapy. We established a GNMT promoter-driven luciferase reporter assay as a drug screening platform. Screening of 324 pure compounds and 480 crude extracts from Chinese medicinal herbs resulted in the identification of Paeonia lactiflora Pall (PL) extract and the active component 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranoside (PGG) as a GNMT inducer...
May 4, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27101439/global-dna-methylation-in-gonads-of-adult-zebrafish-danio-rerio-under-bisphenol-a-exposure
#20
Yan Liu, Yingying Zhang, Shiyu Tao, Yongjing Guan, Ting Zhang, Zaizhao Wang
Altered DNA methylation is pervasively associated with changes in gene expression and signal transduction after exposure to a wide range of endocrine disrupting chemicals. As a weak estrogenic chemical, bisphenol A (BPA) has been extensively studied for reproductive toxicity. In order to explore the effects of BPA on epigenetic modification in gonads of zebrafish Danio rerio, we measured the global DNA methylation together with the gene expression of DNA methyltransferase (dnmts), glycine N-methyltransferase (gnmt), and ten-eleven translocation (tets) in gonads of D...
August 2016: Ecotoxicology and Environmental Safety
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