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role of glutamine

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https://www.readbyqxmd.com/read/29148959/effect-of-measuring-%C3%AE-glutamyl-transpeptidase-and-using-smoflipid-in-a-parenteral-nutrition-infusion-in-a-patient-with-severe-malabsorption-and-overlapping-primary-sclerosing-cholangitis-and-ulcerative-colitis
#1
Merin Kinikini
Studies discussing inflammation and oxidative stress state that these conditions are known contributors in the pathogenesis of cholestatic diseases and ulcerative colitis, and studies examining patients with liver disease have found decreased antioxidant status and significant elevation of lipid peroxides as compared with healthy subjects. One hypothesis in liver disease is that deficient antioxidant defense mechanisms may lead to excess oxygen free radical formation, which promotes deleterious processes in the liver...
November 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29141526/the-in-pancia-study-clinical-evaluation-of-gastrointestinal-dysfunction-and-failure-multiple-organ-failure-and-levels-of-citrulline-in-critically-ill-patients
#2
Nazzareno Fagoni, Simone Piva, Rosella Marino, Giovanni Chiarini, Daniela Ferrari, Eleonora Grespi, Rita Bertuetti, Silvia Barbieri, Nicola Latronico, Frank Rasulo
PURPOSE: Gastrointestinal dysfunction and failure (GID and GIF) in critically ill patients are a common, relevant, and underestimated complications in ICU patients. The aims of this study were (1) to determine plasmatic levels of citrulline, glutamine, and arginine as markers of GID/GIF in critically ill patients with or without GID/GIF with or without multiple organ failure (MOF) and (2) to assess the role of intra-abdominal hypertension in these patient groups. MATERIALS AND METHODS: This is a 1-year, monocentric (Italian hospital), prospective observational study...
January 1, 2017: Journal of Intensive Care Medicine
https://www.readbyqxmd.com/read/29137396/tgfbr-idh1-cav1-axis-promotes-tgf-%C3%AE-signalling-in-cancer-associated-fibroblast
#3
Xiaodan Hou, Jieying Zhang, Yongbin Wang, Wujun Xiong, Jun Mi
TGF-β signalling plays an important role in fibroblasts activation and tumour progression. Here, we report that the TGFBR-IDH1-Cav1 axis promotes TGF- β signalling in fibroblasts. Our data demonstrated that IDH1 was downregulated by TGF-β signalling in fibroblasts, and downregulation of IDH1 increased cellular concentration of α-ketoglutarate (α-KG) by accelerating glutamine metabolization. Interestingly, α-KG suppressed Cav1 expression through reducing the trimethylation of histone H3K4. Furthermore, Cav1 downregulation inhibited TGFBR protein degradation...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29124817/why-the-flavin-dinucleotide-cofactor-needs-to-be-covalently-linked-to-complex-ii-of-the-electron-transport-chain-for-conversion-of-fadh2-to-fad
#4
Daniel F A R Dourado, Marcel Swart, Alexandra Teresa Pires Carvalho
A covalently bound flavin cofactor is predominant in the succinate:ubiquinone oxidoreductase (SQR, Complex II), an essential component of the aerobic electron transport, and in the menaquinol:fumarate oxidoreductase (QFR), the anaerobic counterpart, albeit being only present in ~10% of the known flavoenzymes. Here, we investigated the role of this 8α-N(3)-histidyl linkage between the flavin dinucleotide (FAD) cofactor and the respiratory Complex II. After parameterization with DFT we performed classical molecular dynamics simulations and quantum mechanics calculations of Complex II:FAD and Complex II:FADH2, covalently bound and unbound to His-A57...
November 10, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29120073/astrocytic-and-neuronal-oxidative-metabolism-are-coupled-to-the-rate-of-glutamate-glutamine-cycle-in-the-tree-shrew-visual-cortex
#5
Sarah Sonnay, Jordan Poirot, Nathalie Just, Anne-Catherine Clerc, Rolf Gruetter, Gregor Rainer, João M N Duarte
Astrocytes play an important role in glutamatergic neurotransmission, namely by clearing synaptic glutamate and converting it into glutamine that is transferred back to neurons. The rate of this glutamate-glutamine cycle (VNT ) has been proposed to couple to that of glucose utilization and of neuronal tricarboxylic acid (TCA) cycle. In this study, we tested the hypothesis that glutamatergic neurotransmission is also coupled to the TCA cycle rate in astrocytes. For that we investigated energy metabolism by means of magnetic resonance spectroscopy (MRS) in the primary visual cortex of tree shrews (Tupaia belangeri) under light isoflurane anesthesia at rest and during continuous visual stimulation...
November 9, 2017: Glia
https://www.readbyqxmd.com/read/29119293/asparaginase-erwinia-chrysanthemi-effectively-depletes-plasma-glutamine-in-adult-patients-with-relapsed-refractory-acute-myeloid-leukemia
#6
Ashkan Emadi, Jennie Y Law, Erin T Strovel, Rena G Lapidus, Linda J B Jeng, Myounghee Lee, Miriam G Blitzer, Brandon A Carter-Cooper, Danielle Sewell, Isabella Van Der Merwe, Sunita Philip, Mohammad Imran, Stephen L Yu, Hongxia Li, Philip C Amrein, Vu H Duong, Edward A Sausville, Maria R Baer, Amir T Fathi, Zeba Singh, Søren M Bentzen
Depletion of glutamine (Gln) has emerged as a potential therapeutic approach in the treatment of acute myeloid leukemia (AML), as neoplastic cells require Gln for synthesis of cellular components essential for survival. Asparaginases deplete Gln, and asparaginase derived from Erwinia chrysanthemi (Erwinaze) appears to have the greatest glutaminase activity of the available asparaginases. In this Phase I study, we sought to determine the dose of Erwinaze that safely and effectively depletes plasma Gln levels to ≤ 120 μmol/L in patients with relapsed or refractory (R/R) AML...
November 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29116779/patterns-of-ligands-coordinated-to-metallocofactors-extracted-from-the-protein-data-bank
#7
Luca Belmonte, Sheref S Mansy
A new R tool is described that rapidly identifies, ranks, and clusters sequence patterns coordinated to metallocofactors. This tool, PdPDB, fills a void because unlike currently available tools, PdPDB searches through sequences with metal coordination as the primary determinant and can identify patterns consisting of amino acids, nucleotides, and small molecule ligands at once. PdPDB was tested by analyzing structures that coordinate Fe2+/3+, [2Fe-2S], [4Fe-4S], Zn2+, and Mg2+ cofactors. PdPDB confirmed previously identified sequence motifs and revealed which residues are enriched, e...
November 8, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29116024/systematic-analyses-of-glutamine-and-glutamate-metabolisms-across-different-cancer-types
#8
Yuan Tian, Wei Du, Sha Cao, Yue Wu, Ning Dong, Yan Wang, Ying Xu
BACKGROUND: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types. METHODS: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer...
November 7, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/29109543/penicillin-induces-alterations-in-glutamine-metabolism-in-streptococcus-pneumoniae
#9
Jessica Y El Khoury, Nancy Boucher, Michel G Bergeron, Philippe Leprohon, Marc Ouellette
Penicillin is a bactericidal antibiotic that inhibits the synthesis of the peptidoglycan by targeting penicillin-binding proteins. This study aimed to assess through transcriptional profiling the stress response of S. pneumoniae strains after exposure to lethal penicillin concentrations to understand further the mode of action of penicillin. Two experimental designs (time-course and dose-response) were used for monitoring the effect of penicillin on the transcriptional profile. The expression of some genes previously shown to be modulated by penicillin was altered, including ciaRH, pstS and clpL...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29109155/temporal-fluxomics-reveals-oscillations-in-tca-cycle-flux-throughout-the-mammalian-cell-cycle
#10
Eunyong Ahn, Praveen Kumar, Dzmitry Mukha, Amit Tzur, Tomer Shlomi
Cellular metabolic demands change throughout the cell cycle. Nevertheless, a characterization of how metabolic fluxes adapt to the changing demands throughout the cell cycle is lacking. Here, we developed a temporal-fluxomics approach to derive a comprehensive and quantitative view of alterations in metabolic fluxes throughout the mammalian cell cycle. This is achieved by combining pulse-chase LC-MS-based isotope tracing in synchronized cell populations with computational deconvolution and metabolic flux modeling...
November 6, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/29107960/glutamine-deficiency-induces-dna-alkylation-damage-and-sensitizes-cancer-cells-to-alkylating-agents-through-inhibition-of-alkbh-enzymes
#11
Thai Q Tran, Mari B Ishak Gabra, Xazmin H Lowman, Ying Yang, Michael A Reid, Min Pan, Timothy R O'Connor, Mei Kong
Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH) enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death...
November 2017: PLoS Biology
https://www.readbyqxmd.com/read/29104034/distribution-of-the-branched-chain-%C3%AE-ketoacid-dehydrogenase-complex-e1%C3%AE-subunit-and-glutamate-dehydrogenase-in-the-human-brain-and-their-role-in-neuro-metabolism
#12
Jonathon Hull, Marcela Usmari Moraes, Emma Brookes, Seth Love, Myra E Conway
Glutamate is the major excitatory neurotransmitter of the central nervous system, with the branched-chain amino acids (BCAAs) acting as key nitrogen donors for de novo glutamate synthesis. Despite the importance of these major metabolites, their metabolic pathway in the human brain is still not well characterised. The metabolic pathways that influence the metabolism of BCAAs have been well characterised in rat models. However, the expression of key proteins such as the branched-chain α-ketoacid dehydrogenase (BCKD) complex and glutamate dehydrogenase isozymes (GDH) in the human brain is still not well characterised...
November 9, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29098534/impairment-of-astrocytic-glutaminolysis-in-glutaric-aciduria-type-i
#13
Shoko Komatsuzaki, Raga Deepthi Ediga, Jürgen G Okun, Stefan Kölker, Sven W Sauer
Glutaric aciduria type I is a rare, autosomal recessive, inherited defect of glutaryl-CoA dehydrogenase. Deficiency of this protein in L-lysine degradation leads to the characteristic accumulation of nontoxic glutarylcarnitine and neurotoxic glutaric acid (GA), glutaryl-CoA, and 3-hydroxyglutaric acid. Untreated patients develop bilateral lesions of basal ganglia resulting in a complex movement disorder with predominant dystonia in infancy and early childhood. The current pathomechanistic concept strongly focuses on imbalanced neuronal energy metabolism due to accumulating metabolites, whereas little is known about the pathomechanistic role of astrocytes, which are thought to be in constant metabolic crosstalk with neurons...
November 2, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29097210/mir-137-inhibits-glutamine-catabolism-and-growth-of-malignant-melanoma-by-targeting-glutaminase
#14
Wenkang Luan, Zhou Zhou, Yan Zhu, Yun Xia, Jinlong Wang, Bin Xu
Glutamine catabolism is considered to be an important metabolic pathway for cancer cells. Glutaminase (GLS) is the important rate-limiting enzyme of glutamine catabolism. miR-137 functions as a tumor suppressor in many human malignant tumors. However, the role and molecular mechanism of miR-137 and GLS in malignant melanoma has not been reported. In this study, we showed that miR-137 was decreased in melanoma tissue, and the low miR-137 level and high GLS expression are independent risk factor in melanoma. miR-137 suppressed the proliferation and glutamine catabolism of melanoma cells...
October 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29062270/the-glyr-extracellular-%C3%AE-8-%C3%AE-9-loop-a-functional-determinant-of-agonist-potency
#15
Dieter Janzen, Natascha Schaefer, Carolyn Delto, Hermann Schindelin, Carmen Villmann
Ligand-binding of Cys-loop receptors results in rearrangements of extracellular loop structures which are further translated into the tilting of membrane spanning helices, and finally opening of the ion channels. The cryo-EM structure of the homopentameric α1 glycine receptor (GlyR) demonstrated an involvement of the extracellular β8-β9 loop in the transition from ligand-bound receptors to the open channel state. Recently, we identified a functional role of the β8-β9 loop in a novel startle disease mouse model shaky...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29053708/ssn6-tup1-global-transcriptional-co-repressor-role-of-the-n-terminal-glutamine-rich-region-of-ssn6
#16
Athanassios Tartas, Christoforos Zarkadas, Maria Palaiomylitou, Niki Gounalaki, Dimitris Tzamarias, Metaxia Vlassi
The Ssn6-Tup1 complex is a general transcriptional co-repressor formed by the interaction of Ssn6, a tetratricopeptide repeat (TPR) protein, with the Tup1 repressor. We have previously shown that the N-terminal domain of Ssn6 comprising TPRs 1 to 3 is necessary and sufficient for this interaction and that TPR1 plays critical role. In a subsequent study, we provided evidence that in the absence of Tup1, TPR1 is susceptible to proteolysis and that conformational change(s) accompany the Ssn6-Tup1 complex formation...
2017: PloS One
https://www.readbyqxmd.com/read/29052795/effects-of-glutamine-taurine-and-their-association-on-inflammatory-pathway-markers-in-macrophages
#17
Talita Sartori, Guilherme Galvão Dos Santos, Amanda Nogueira-Pedro, Edson Makiyama, Marcelo Macedo Rogero, Primavera Borelli, Ricardo Ambrósio Fock
The immune system is essential for the control and elimination of infections, and macrophages are cells that act as important players in orchestrating the various parts of the inflammatory/immune response. Amino acids play important role in mediating functionality of the inflammatory response, especially mediating macrophages functions and cytokines production. We investigated the influence of glutamine, taurine and their association on the modulation of inflammatory pathway markers in macrophages. The RAW 264...
October 20, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/29046333/the-p53-inducible-long-noncoding-rna-trings-protects-cancer-cells-from-necrosis-under-glucose%C3%A2-starvation
#18
Muhammad Riaz Khan, Shaoxun Xiang, Zhiyin Song, Mian Wu
The tumor suppressor p53 is activated in response to cellular stress to prevent malignant transformation. However, several recent studies have shown that p53 can play protective roles in tumor cell survival under adversity. Whether p53-regulated long noncoding RNAs are involved in this process remains to be fully understood. Here, we show that under glucose starvation condition, p53 directly upregulates a novel lncRNA named TRINGS (Tp53-regulated inhibitor of necrosis under glucose starvation) in human tumor cells...
October 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29034927/exploring-the-role-of-gs-gogat-cycle-in-microcystin-synthesis-and-regulation-a-model-based-analysis
#19
Swarnendu Banerjee, Abhishek Subramanian, Joydev Chattopadhyay, Ram Rup Sarkar
Toxic cyanobacteria blooms populate water bodies by consuming external nutrients and releasing cyanotoxins that are detrimental for other aquatic species, producing a significant impact on the plankton ecosystem and food web. To exercise population-level control of toxin production, understanding the biochemical mechanisms that explain cyanotoxin regulation within a bacterial cell is of utmost importance. In this study, we explore the mechanistic events to investigate the dependence of toxin microcystin on external nitrogen, a known regulator of the toxin, and for the first time, propose a kinetic model that analyzes the intracellular conditions required to ensure nitrogen dependence on microcystin...
October 16, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/29031723/inhibition-of-cholinergic-potentiation-of-insulin-secretion-from-pancreatic-islets-by-chronic-elevation-of-glucose-and-fatty-acids-protection-by-casein-kinase-2-inhibitor
#20
Nicolai M Doliba, Qin Liu, Changhong Li, Pan Chen, Chengyang Liu, Ali Naji, Franz M Matschinsky
OBJECTIVES: Chronic hyperlipidemia and hyperglycemia are characteristic features of type 2 diabetes (T2DM) that are thought to cause or contribute to β-cell dysfunction by "glucolipotoxicity." Previously we have shown that acute treatment of pancreatic islets with fatty acids (FA) decreases acetylcholine-potentiated insulin secretion. This acetylcholine response is mediated by M3 muscarinic receptors, which play a key role in regulating β-cell function. Here we examine whether chronic FA exposure also inhibits acetylcholine-potentiated insulin secretion using mouse and human islets...
October 2017: Molecular Metabolism
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