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asparagine synthetase

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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
#1
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...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27866376/reduction-in-dietary-acrylamide-exposure-impact-of-potatoes-with-low-acrylamide-potential
#2
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
#3
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...
October 17, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27743885/the-first-report-of-japanese-patients-with-asparagine-synthetase-deficiency
#4
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...
October 12, 2016: Brain & Development
https://www.readbyqxmd.com/read/27677693/unexpected-functional-implication-of-a-stable-succinimide-in-the-structural-stability-of-methanocaldococcus-jannaschii-glutaminase
#5
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
#6
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
#7
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
#8
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
#9
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
#10
Chi Chun Wong, Yun Qian, Xiaona Li, Jiaying Xu, Wei Kang, Joanna H Tong, Ka-Fai To, Ye Jin, Weilin Li, Huarong Chen, Minnie Yy Go, Jian-Lin Wu, Ka Wing Cheng, Simon Sm Ng, Joseph Jy Sung, Zongwei Cai, Jun Yu
BACKGROUND & AIMS: Many colorectal cancer (CRC) cells contain mutations in KRAS. Analyses of colorectal cancer 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 colorectal cancer cells with mutations in KRAS. METHODS: We measured levels of SLC25A22 mRNA 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...
July 20, 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
#11
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
#12
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
#13
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...
2016: BMC Neurology
https://www.readbyqxmd.com/read/27312010/filamentation-of-metabolic-enzymes-in-saccharomyces-cerevisiae
#14
Qing-Ji Shen, Hakimi Kassim, Yong Huang, Hui Li, Jing Zhang, Guang Li, Peng-Ye Wang, Jun Yan, Fangfu Ye, Ji-Long Liu
Compartmentation via filamentation has recently emerged as a novel mechanism for metabolic regulation. In order to identify filament-forming metabolic enzymes systematically, we performed a genome-wide screening of all strains available from an open reading frame-GFP collection in Saccharomyces cerevisiae. We discovered nine novel filament-forming proteins and also confirmed those identified previously. From the 4159 strains, we found 23 proteins, mostly metabolic enzymes, which are capable of forming filaments in vivo...
June 20, 2016: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/27268761/worsening-of-seizures-after-asparagine-supplementation-in-a-child-with-asparagine-synthetase-deficiency
#15
Muhammad Talal Alrifai, Majid Alfadhel
OBJECTIVE: Asparagine synthetase deficiency is an autosomal recessive neurometabolic disorder characterized clinically by severe congenital microcephaly, global developmental delay, intractable epilepsy, and motor impairment in the form of spastic quadriparesis. Diagnosis is confirmed by findings of low cerebral spinal fluid or plasma asparagine in addition to a mutation of the subsequently in ASNS gene. There is no documented trial of asparagine as a treatment for this disorder. PATIENT DESCRIPTION: We present a child with asparagine synthetase deficiency whose mental status improved slightly from a vegetative state to a minimally conscious state after starting asparagine supplementation...
May 2016: Pediatric Neurology
https://www.readbyqxmd.com/read/27251594/knockdown-of-asparagine-synthetase-asns-suppresses-cell-proliferation-and-inhibits-tumor-growth-in-gastric-cancer-cells
#16
Qingxiang Yu, Xiaoyu Wang, Li Wang, Jia Zheng, Jiang Wang, Bangmao Wang
OBJECTIVE: Asparagine synthetase (ASNS) gene encodes an enzyme that catalyzes the glutamine- and ATP-dependent conversion of aspartic acid to asparagine. ASNS is deemed as a promising therapeutic target and its expression is associated with the chemotherapy resistance in several human cancers. However, its role in gastric cancer tumorigenesis has not been investigated. METHODS: In this study, we employed small interfering RNA (siRNA) to transiently knockdown ASNS in two gastric cancer cell lines, AGS and MKN-45, followed by growth rate assay and colony formation assay...
October 2016: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/27239448/pre-mrna-splicing-is-modulated-by-antifungal-drugs-in-the-filamentous-fungus-neurospora-crassa
#17
Niege S Mendes, Patricia M Silva, Rafael Silva-Rocha, Nilce M Martinez-Rossi, Antonio Rossi
For this study, we sought to identify pre-mRNA processing events modulated by changes in extracellular pH, inorganic phosphate, and antifungal drugs. We examined genes with at least four putative introns whose transcriptional level responded to these effectors. We showed that the intron retention levels of genes encoding asparagine synthetase 2, C6-zinc finger regulator (fluffy), and a farnesyltransferase respond to amphotericin B, ketoconazole, and other effectors. In general, the assayed antifungals promoted the disruption of the structural domains of these proteins probably leading to their inactivation, which emphasize the complexity of the metabolic modulation exerted by antifungal signaling...
April 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/27168155/integration-of-lupinus-angustifolius-l-narrow-leafed-lupin-genome-maps-and-comparative-mapping-within-legumes
#18
Katarzyna Wyrwa, Michał Książkiewicz, Anna Szczepaniak, Karolina Susek, Jan Podkowiński, Barbara Naganowska
Narrow-leafed lupin (Lupinus angustifolius L.) has recently been considered a reference genome for the Lupinus genus. In the present work, genetic and cytogenetic maps of L. angustifolius were supplemented with 30 new molecular markers representing lupin genome regions, harboring genes involved in nitrogen fixation during the symbiotic interaction of legumes and soil bacteria (Rhizobiaceae). Our studies resulted in the precise localization of bacterial artificial chromosomes (BACs) carrying sequence variants for early nodulin 40, nodulin 26, nodulin 45, aspartate aminotransferase P2, asparagine synthetase, cytosolic glutamine synthetase, and phosphoenolpyruvate carboxylase...
September 2016: Chromosome Research
https://www.readbyqxmd.com/read/27126896/asparagine-promotes-cancer-cell-proliferation-through-use-as-an-amino-acid-exchange-factor
#19
Abigail S Krall, Shili Xu, Thomas G Graeber, Daniel Braas, Heather R Christofk
Cellular amino acid uptake is critical for mTOR complex 1 (mTORC1) activation and cell proliferation. However, the regulation of amino acid uptake is not well-understood. Here we describe a role for asparagine as an amino acid exchange factor: intracellular asparagine exchanges with extracellular amino acids. Through asparagine synthetase knockdown and altering of media asparagine concentrations, we show that intracellular asparagine levels regulate uptake of amino acids, especially serine, arginine and histidine...
2016: Nature Communications
https://www.readbyqxmd.com/read/27110058/food-safety-structure-and-expression-of-the-asparagine-synthetase-gene-family-of-wheat
#20
Runhong Gao, Tanya Y Curtis, Stephen J Powers, Hongwei Xu, Jianhua Huang, Nigel G Halford
Asparagine is an important nitrogen storage and transport molecule, but its accumulation as a free amino acid in crops has implications for food safety because free asparagine is a precursor for acrylamide formation during cooking and processing. Asparagine synthesis occurs by the amidation of aspartate, catalysed by asparagine synthetase, and this study concerned the expression of asparagine synthetase (TaASN) genes in wheat. The expression of three genes, TaASN1-3, was studied in different tissues and in response to nitrogen and sulphur supply...
March 2016: Journal of Cereal Science
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