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asparagine synthetase

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https://www.readbyqxmd.com/read/28642445/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#1
Salvatore Nicola Bertuccio, Salvatore Serravalle, Annalisa Astolfi, Annalisa Lonetti, Valentina Indio, Anna Leszl, Andrea Pession, Fraia Melchionda
L-Asparaginase (L-Asp) is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid, and its depletion induces leukemic cell death. L-Asp is an important component of treatment regimens for Acute Lymphoblastic Leukemia (ALL). Sensitivity to L-Asp is due to the absence of L-Asparagine synthetase (ASNS), the enzyme that catalyzes the biosynthesis of L-asparagine. ASNS gene is located on 7q21.3, and its increased expression in ALLs correlates with L-Asp resistance. Chromosome 7 monosomy (-7) is a recurrent aberration in myeloid disorders, particularly in adverse-risk Acute Myeloid Leukemias (AMLs) and therapy-related myeloid neoplasms (t-MN), that leads to a significant downregulation of the deleted genes, including ASNS...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28629319/polymorphism-in-asparagine-synthetase-is-associated-with-overall-survival-of-hepatocellular-carcinoma-patients
#2
Wei Li, Chengwei Dong
BACKGROUND: Recently, it is reported that asparagine synthetase (ASNS) is an independent predictor of surgical survival in hepatocellular carcinoma (HCC) patients. It is also reported that activating transcription factor 6 (ATF6) expression is decreased in HCC patients. So in the present study, we explored the relationship between ASNS and ATF6, and whether ASNS expression was associated with HCC. METHODS: ATF6 was over expressed in 3 HCC cell lines (HepG2, HepG2...
June 19, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28525813/ammonia-stress-on-nitrogen-metabolism-in-tolerant-aquatic-plant-myriophyllum-aquaticum
#3
Qingyang Zhou, Jingqing Gao, Ruimin Zhang, Ruiqin Zhang
Ammonia has been a major reason of macrophyte decline in the water environment, and ammonium ion toxicity should be seen as universal, even in species frequently labeled as "NH4(+) specialists". To study the effects of high NH4(+)-N stress of ammonium ion nitrogen on tolerant submerged macrophytes and investigate the pathways of nitrogen assimilation in different organisms, Myriophyllum aquaticum was selected and treated with various concentrations of ammonium ions at different times. Increasing of ammonium concentration leads to an overall increase in incipient ammonia content in leaves and stems of plants...
May 16, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28390103/asn1-encoded-asparagine-synthetase-in-floral-organs-contributes-to-nitrogen-filling-in-arabidopsis-seeds
#4
Laure Gaufichon, Anne Marmagne, Katia Belcram, Tadakatsu Yoneyama, Yukiko Sakakibara, Toshiharu Hase, Olivier Grandjean, Gilles Clément, Sylvie Citerne, Stéphanie Boutet-Mercey, Céline Masclaux-Daubresse, Fabien Chardon, Fabienne Soulay, Xiaole Xu, Marion Trassaert, Maryam Shakiebaei, Amina Najihi, Akira Suzuki
Despite a general view that asparagine synthetase generates asparagine as an amino acid for long-distance transport of nitrogen to sink organs, its role in nitrogen metabolic pathways in floral organs during seed nitrogen filling has remained undefined. We demonstrate that the onset of pollination in Arabidopsis induces selected genes for asparagine metabolism, namely ASN1 (At3g47340), GLN2 (At5g35630), GLU1 (At5g04140), AapAT2 (At5g19950), ASPGA1 (At5g08100) and ASPGB1 (At3g16150), particularly at the ovule stage (stage 0), accompanied by enhanced asparagine synthetase protein, asparagine and total amino acids...
April 8, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28358347/the-enzymology-of-2-hydroxyglutarate-2-hydroxyglutaramate-and-2-hydroxysuccinamate-and-their-relationship-to-oncometabolites
#5
Vivek A Hariharan, Travis T Denton, Sarah Paraszcszak, Kyle McEvoy, Thomas M Jeitner, Boris F Krasnikov, Arthur J L Cooper
Many enzymes make "mistakes". Consequently, repair enzymes have evolved to correct these mistakes. For example, lactate dehydrogenase (LDH) and mitochondrial malate dehydrogenase (mMDH) slowly catalyze the reduction of 2-oxoglutarate (2-OG) to the oncometabolite l-2-hydroxyglutarate (l-2-HG). l-2-HG dehydrogenase corrects this error by converting l-2-HG to 2-OG. LDH also catalyzes the reduction of the oxo group of 2-oxoglutaramate (2-OGM; transamination product of l-glutamine). We show here that human glutamine synthetase (GS) catalyzes the amidation of the terminal carboxyl of both the l- and d- isomers of 2-HG...
March 30, 2017: Biology
https://www.readbyqxmd.com/read/28245795/in-search-of-druggable-targets-for-gbm-amino-acid-metabolism
#6
Eduard H Panosyan, Henry J Lin, Jan Koster, Joseph L Lasky
BACKGROUND: Amino acid (AA) pathways may contain druggable targets for glioblastoma (GBM). Literature reviews and GBM database ( http://r2.amc.nl ) analyses were carried out to screen for such targets among 95 AA related enzymes. METHODS: First, we identified the genes that were differentially expressed in GBMs (3 datasets) compared to non-GBM brain tissues (5 datasets), or were associated with survival differences. Further, protein expression for these enzymes was also analyzed in high grade gliomas (HGGs) (proteinatlas...
February 28, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28197753/asparaginase-pharmacology-challenges-still-to-be-faced
#7
REVIEW
Claudia Lanvers-Kaminsky
PURPOSE: The benefits of asparaginase (ASNASE) in the treatment of ALL and NHL are indisputable and new ASNASE preparations are under clinical development to overcome limitations of the actual ASNASE therapy, especially immunogenicity. Apart from ALL and NHL further indications of ASNASE are preclinically and clinically evaluated. METHODS: We reviewed ASNASE literature and especially focused on the mechanism of action, on biomarker, which determine ASNASE sensitivity and resistance, and on ASNASE pharmacodynamics in vivo...
March 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27913282/proteomics-provides-insights-into-biological-pathways-altered-by-plant-growth-promoting-bacteria-and-arbuscular-mycorrhiza-in-sorghum-grown-in-marginal-soil
#8
Faten Dhawi, Rupali Datta, Wusirika Ramakrishna
Sorghum is an economically important crop, a model system for gene discovery and a biofuel source. Sorghum seedlings were subjected to three microbial treatments, plant growth promoting bacteria (B), arbuscular mycorrhizal (AM) fungi mix with two Glomus species (G. aggregatum and G. etunicatum), Funelliformis mosseae and Rhizophagus irregularis (My), and B and My combined (My+B). Proteomic analysis was conducted followed by integration with metabolite, plant biomass and nutrient data. Out of 366 differentially expressed proteins in sorghum roots, 44 upregulated proteins overlapping among three treatment groups showed positive correlation with sorghum biomass or element uptake or both...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27866376/reduction-in-dietary-acrylamide-exposure-impact-of-potatoes-with-low-acrylamide-potential
#9
Nga L Tran, Leila M Barraj, Susan Collinge
Acrylamide forms primarily from a reaction between reducing sugars (e.g., glucose and fructose) and an amino acid (asparagine, Asn) formed naturally in foods, including potatoes. This reaction occurs when carbohydrate-rich foods are heated at temperatures above 120 °C. Multiple potato varieties were transformed with potato genomic DNA that results in down-regulation of the expression of the asparagine synthetase-1 gene (Asn1), significantly reducing synthesis of free Asn, and consequently lowering the potential to form acrylamide during cooking...
November 20, 2016: Risk Analysis: An Official Publication of the Society for Risk Analysis
https://www.readbyqxmd.com/read/27764698/metabolic-alterations-caused-by-kras-mutations-in-colorectal-cancer-contribute-to-cell-adaptation-to-glutamine-depletion-by-upregulation-of-asparagine-synthetase
#10
Kosuke Toda, Kenji Kawada, Masayoshi Iwamoto, Susumu Inamoto, Takehiko Sasazuki, Senji Shirasawa, Suguru Hasegawa, Yoshiharu Sakai
A number of clinical trials have shown that KRAS mutations of colorectal cancer (CRC) can predict a lack of responses to anti-epidermal growth factor receptor-based therapy. Recently, there have been several studies to elucidate metabolism reprogramming in cancer. However, it remains to be investigated how mutated KRAS can coordinate the metabolic shift to sustain CRC tumor growth. In this study, we found that KRAS mutation in CRC caused alteration in amino acid metabolism. KRAS mutation causes a marked decrease in aspartate level and an increase in asparagine level in CRC...
November 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27743885/the-first-report-of-japanese-patients-with-asparagine-synthetase-deficiency
#11
Takahiro Yamamoto, Wakaba Endo, Hidenori Ohnishi, Kazuo Kubota, Norio Kawamoto, Takehiko Inui, Atsushi Imamura, Jun-Ichi Takanashi, Masaaki Shiina, Hirotomo Saitsu, Kazuhiro Ogata, Naomichi Matsumoto, Kazuhiro Haginoya, Toshiyuki Fukao
BACKGROUND: Asparagine synthetase (ASNS) deficiency was recently discovered as a metabolic disorder of non-essential amino acids, and presents as severe progressive microcephaly, intellectual disorder, dyskinetic quadriplegia, and intractable seizures. METHODS: Two Japanese children with progressive microcephaly born to unrelated patients were analyzed by whole exome sequencing and novel ASNS mutations were identified. The effects of the ASNS mutations were analyzed by structural evaluation and in silico predictions...
March 2017: Brain & Development
https://www.readbyqxmd.com/read/27677693/unexpected-functional-implication-of-a-stable-succinimide-in-the-structural-stability-of-methanocaldococcus-jannaschii-glutaminase
#12
Sanjeev Kumar, Sunita Prakash, Kallol Gupta, Aparna Dongre, Padmanabhan Balaram, Hemalatha Balaram
Protein ageing is often mediated by the formation of succinimide intermediates. These short-lived intermediates derive from asparaginyl deamidation and aspartyl dehydration and are rapidly converted into β-aspartyl or D-aspartyl residues. Here we report the presence of a highly stable succinimide intermediate in the glutaminase subunit of GMP synthetase from the hyperthermophile Methanocaldoccocus jannaschii. By comparing the biophysical properties of the wild-type protein and of several mutants, we show that the presence of succinimide increases the structural stability of the glutaminase subunit...
2016: Nature Communications
https://www.readbyqxmd.com/read/27668749/identification-of-genome-wide-mutations-in-ciprofloxacin-resistant-f-tularensis-lvs-using-whole-genome-tiling-arrays-and-next-generation-sequencing
#13
Crystal J Jaing, Kevin S McLoughlin, James B Thissen, Adam Zemla, Shea N Gardner, Lisa M Vergez, Feliza Bourguet, Shalini Mabery, Viacheslav Y Fofanov, Heather Koshinsky, Paul J Jackson
Francisella tularensis is classified as a Class A bioterrorism agent by the U.S. government due to its high virulence and the ease with which it can be spread as an aerosol. It is a facultative intracellular pathogen and the causative agent of tularemia. Ciprofloxacin (Cipro) is a broad spectrum antibiotic effective against Gram-positive and Gram-negative bacteria. Increased Cipro resistance in pathogenic microbes is of serious concern when considering options for medical treatment of bacterial infections. Identification of genes and loci that are associated with Ciprofloxacin resistance will help advance the understanding of resistance mechanisms and may, in the future, provide better treatment options for patients...
2016: PloS One
https://www.readbyqxmd.com/read/27551855/differential-gel-electrophoresis-dige-evaluation-of-naphthoimidazoles-mode-of-action-a-study-in-trypanosoma-cruzi-bloodstream-trypomastigotes
#14
Giselle Villa Flor Brunoro, Vitor Marcel Faça, Marcelle Almeida Caminha, André Teixeira da Silva Ferreira, Monique Trugilho, Kelly Cristina Gallan de Moura, Jonas Perales, Richard Hemmi Valente, Rubem Figueiredo Sadok Menna-Barreto
BACKGROUND: The obligate intracellular protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a neglected illness affecting millions of people in Latin America that recently entered non-endemic countries through immigration, as a consequence of globalization. The chemotherapy for this disease is based mainly on benznidazole and nifurtimox, which are very efficient nitroderivatives against the acute stage but present limited efficacy during the chronic phase. Our group has been studying the trypanocidal effects of naturally occurring quinones and their derivatives, and naphthoimidazoles derived from β-lapachone N1, N2 and N3 were the most active...
August 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27522229/epileptic-phenotype-of-two-siblings-with-asparagine-synthesis-deficiency-mimics-neonatal-pyridoxine-dependent-epilepsy
#15
Svetlana Gataullina, Julia Lauer-Zillhardt, Anna Kaminska, Louise Galmiche-Rolland, Nadia Bahi-Buisson, Clément Pontoizeau, Chris Ottolenghi, Olivier Dulac, Catherine Fallet-Bianco
We report the cases of a brother and a sister of nonconsanguineous parents who developed progressive microcephaly and had tremor, irritability, spasticity, startle reflexes, and permanent erratic myoclonus since birth. Focal clonic seizures, status epilepticus, and infantile spasms appeared later, during the first months of life, while erratic myoclonic jerks persisted. Electroencephalogram initially showed multifocal spikes that evolved into modified hypsarrhythmia and then discontinuous activity, evoking the progressive nature of the condition...
December 2016: Neuropediatrics
https://www.readbyqxmd.com/read/27469131/diaphragmatic-eventration-in-sisters-with-asparagine-synthetase-deficiency-a-novel-homozygous-asns-mutation-and-expanded-phenotype
#16
Jun Sun, Angela J McGillivray, Jason Pinner, Zhihui Yan, Fengxia Liu, Drago Bratkovic, Elizabeth Thompson, Xiuxiu Wei, Huifeng Jiang, Asan, Maya Chopra
BACKGROUND: Asparagine Synthetase Deficiency (ASNSD; OMIM #615574) is a newly described rare autosomal recessive neurometabolic disorder, characterised by congenital microcephaly, severe psychomotor delay, encephalopathy and progressive cerebral atrophy. To date, seven families and seven missense mutations in the ASNSD disease causing gene, ASNS, have been published. METHODS: We report two further affected infant sisters from a consanguineous Indian family, who in addition to the previously described features had diaphragmatic eventration...
July 27, 2016: JIMD Reports
https://www.readbyqxmd.com/read/27451147/slc25a22-promotes-proliferation-and-survival-of-colorectal-cancer-cells-with-kras-mutations-and-xenograft-tumor-progression-in-mice-via-intracellular-synthesis-of-aspartate
#17
Chi Chun Wong, Yun Qian, Xiaona Li, Jiaying Xu, Wei Kang, Joanna H Tong, Ka-Fai To, Ye Jin, Weilin Li, Huarong Chen, Minnie Y Y Go, Jian-Lin Wu, Ka Wing Cheng, Simon S M Ng, Joseph J Y Sung, Zongwei Cai, Jun Yu
BACKGROUND & AIMS: Many colorectal cancer (CRC) cells contain mutations in KRAS. Analyses of CRC cells with mutations in APC or CTNNB1 and KRAS identified SLC25A22, which encodes mitochondrial glutamate transporter, as a synthetic lethal gene. We investigated the functions of SLC25A22 in CRC cells with mutations in KRAS. METHODS: We measured levels of SLC25A22 messenger RNA and protein in paired tumor and nontumor colon tissues collected from 130 patients in Hong Kong and 17 patients in China and compared protein levels with patient survival times...
November 2016: Gastroenterology
https://www.readbyqxmd.com/read/27446147/changes-in-free-amino-acid-concentration-in-rye-grain-in-response-to-nitrogen-and-sulfur-availability-and-expression-analysis-of-genes-involved-in-asparagine-metabolism
#18
Jennifer Postles, Tanya Y Curtis, Stephen J Powers, J S Elmore, Donald S Mottram, Nigel G Halford
Free asparagine plays a central role in nitrogen storage and transport in many plant species due to its relatively high ratio of nitrogen to carbon. However, it is also a precursor for acrylamide, a Class 2a carcinogen that forms during high-temperature processing and cooking. The concentration of free asparagine was shown to increase by approximately 70% in rye grain in response to severe sulfur deficiency (F-test, p = 0.004), while the concentration of both free asparagine and free glutamine increased (by almost threefold and approximately 62%, respectively) in response to nitrogen application (F-test, p < 0...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27444726/loss-of-asparagine-synthetase-suppresses-the-growth-of-human-lung-cancer-cells-by-arresting-cell-cycle-at-g0-g1-phase
#19
Yi Xu, Fanzhen Lv, Xunxia Zhu, Yun Wu, Xiaoyong Shen
The aim of this research is to determine the role of human asparagine synthetase (ASNS) in human lung cancer. In the present study, immunohistochemical staining and the Oncomine database mining showed that the expression of ASNS gene was higher in lung cancer tissues than that in the normal tissues by. In addition, western blot assay showed that ASNS was elevated in lung cancer A549 and 95D cell lines as compared with that in H1299 and H460 cells. Therefore, A549 and 95D cells were chosen for subsequent MTT and colony formation assay...
September 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27422383/hyperekplexia-microcephaly-and-simplified-gyral-pattern-caused-by-novel-asns-mutations-case-report
#20
Mohammed Zain Seidahmed, Mustafa A Salih, Omer B Abdulbasit, Abdulmohsen Samadi, Khalid Al Hussien, Abeer M Miqdad, Maha S Biary, Anas M Alazami, Ibrahim A Alorainy, Mohammad M Kabiraj, Ranad Shaheen, Fowzan S Alkuraya
BACKGROUND: Asparagine synthetase deficiency (OMIM# 615574) is a very rare newly described neurometabolic disorder characterized by congenital microcephaly and severe global developmental delay, associated with intractable seizures or hyperekplexia. Brain MRI typically shows cerebral atrophy with simplified gyral pattern and delayed myelination. Only 12 cases have been described to date. The disease is caused by homozygous or compound heterozygous mutations in the ASNS gene on chromosome 7q21...
July 15, 2016: BMC Neurology
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