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| L-glutamine |
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| CHEBI:18050 |
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| L-glutamine |
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| An optically active form of glutamine having L-configuration. |
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This entity has been manually annotated by the ChEBI Team.
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CHEBI:21308, CHEBI:42899, CHEBI:42812, CHEBI:42814, CHEBI:42943, CHEBI:6227, CHEBI:13110
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| ChemicalBook:CB14796928, ChemicalBook:CB34867000, ChemicalBook:CB6280105, eMolecules:514487, Selleckchem:Glutamine, ZINC000001532526 |
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Molfile
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more structures >>
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call loadScript javascripts\jsmol\core\package.js call loadScript javascripts\jsmol\core\core.z.js -- required by ClazzNode call loadScript javascripts\jsmol\J\awtjs2d\WebOutputChannel.js Jmol JavaScript applet jmolApplet0_object__665292255720918__ initializing getValue debug = null getValue logLevel = null getValue allowjavascript = null AppletRegistry.checkIn(jmolApplet0_object__665292255720918__) call loadScript javascripts\jsmol\core\corestate.z.js viewerOptions: { "name":"jmolApplet0_object","applet":true,"documentBase":"https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:18050","platform":"J.awtjs2d.Platform","fullName":"jmolApplet0_object__665292255720918__","display":"jmolApplet0_canvas2d","signedApplet":"true","appletReadyCallback":"Jmol._readyCallback","statusListener":"[J.appletjs.Jmol.MyStatusListener object]","codeBase":"https://www.ebi.ac.uk/chebi/javascripts/jsmol/","syncId":"665292255720918","bgcolor":"#000" } (C) 2012 Jmol Development Jmol Version: 13.2.7 $Date: 2013-10-01 11:35:15 -0500 (Tue, 01 Oct 2013) $ java.vendor: j2s java.version: 0.0 os.name: j2s Access: ALL memory: 0.0/0.0 processors available: 1 useCommandThread: false appletId:jmolApplet0_object (signed) starting HoverWatcher_1 getValue emulate = null defaults = "Jmol" getValue boxbgcolor = null getValue bgcolor = #000 backgroundColor = "#000" getValue ANIMFRAMECallback = null getValue APPLETREADYCallback = Jmol._readyCallback APPLETREADYCallback = "Jmol._readyCallback" getValue ATOMMOVEDCallback = null getValue CLICKCallback = null getValue ECHOCallback = null getValue ERRORCallback = null getValue EVALCallback = null getValue HOVERCallback = null getValue LOADSTRUCTCallback = null getValue MEASURECallback = null getValue MESSAGECallback = null getValue MINIMIZATIONCallback = null getValue PICKCallback = null getValue RESIZECallback = null getValue SCRIPTCallback = null getValue SYNCCallback = null getValue STRUCTUREMODIFIEDCallback = null getValue doTranslate = null language=en_US getValue popupMenu = null getValue script = null Jmol applet jmolApplet0_object__665292255720918__ ready call loadScript javascripts\jsmol\core\corescript.z.js call loadScript javascripts\jsmol\J\script\FileLoadThread.js starting QueueThread0_2 script 1 started starting HoverWatcher_3 starting HoverWatcher_4 The Resolver thinks Mol Marvin 12270700273D starting HoverWatcher_5 Time for openFile( Marvin 12270700273D 20 19 0 0 1 0 999 V2000 -2.1880 1.1172 -0.0951 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2620 0.1322 -0.6210 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1298 -0.1851 0.3902 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8860 -1.2434 -0.1154 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9500 -1.4881 0.8338 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3663 0.8495 0.0900 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7992 2.2437 0.1975 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6898 0.6037 -1.8920 N 0 0 0 0 0 0 0 0 0 0 0 0 2.7222 -0.5334 1.2035 N 0 0 0 0 0 0 0 0 0 0 0 0 2.1324 -2.5992 1.3092 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7900 -0.8009 -0.8417 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5703 -0.5405 1.3282 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4036 0.7440 0.6184 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3442 -2.1663 -0.3442 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3445 -0.9078 -1.0496 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3431 2.8413 0.5448 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4543 0.8162 -2.5346 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1872 1.4736 -1.7016 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3998 -0.6818 1.8287 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5974 0.3251 0.8509 H 0 0 0 0 0 0 0 0 0 0 0 0 2 1 1 0 0 0 0 7 1 1 0 0 0 0 6 1 2 0 0 0 0 3 2 1 0 0 0 0 2 8 1 0 0 0 0 4 3 1 0 0 0 0 5 4 1 0 0 0 0 9 5 1 0 0 0 0 10 5 2 0 0 0 0 2 11 1 0 0 0 0 3 12 1 0 0 0 0 3 13 1 0 0 0 0 4 14 1 0 0 0 0 4 15 1 0 0 0 0 7 16 1 0 0 0 0 8 17 1 0 0 0 0 8 18 1 0 0 0 0 9 19 1 0 0 0 0 9 20 1 0 0 0 0 M END): 22 ms reading 20 atoms ModelSet: haveSymmetry:false haveUnitcells:false haveFractionalCoord:false 1 model in this collection. Use getProperty "modelInfo" or getProperty "auxiliaryInfo" to inspect them. Default Van der Waals type for model set to Babel 20 atoms created ModelSet: not autobonding; use forceAutobond=true to force automatic bond creation Script completed Jmol script terminated
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| Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, polar amino acid. It is non-essential and conditionally essential in humans, meaning the body can usually synthesize sufficient amounts of it, but in some instances of stress, the body's demand for glutamine increases, and glutamine must be obtained from the diet. It is encoded by the codons CAA and CAG. It is named after glutamic acid, which in turn is named after its discovery in cereal proteins, gluten.
In human blood, glutamine is the most abundant free amino acid.
The dietary sources of glutamine include especially the protein-rich foods like beef, chicken, fish, dairy products, eggs, vegetables like beans, beets, cabbage, spinach, carrots, parsley, vegetable juices and also in wheat, papaya, Brussels sprouts, celery, kale and fermented foods like miso.
The one-letter symbol Q for glutamine was assigned in alphabetical sequence to N for asparagine, being larger by merely one methylene –CH2– group. Note that P was used for proline, and O was avoided due to similarity with D. The mnemonic Qlutamine was also proposed. |
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Read full article at Wikipedia
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| InChI=1S/C5H10N2O3/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H2,7,8)(H,9,10)/t3-/m0/s1 |
| ZDXPYRJPNDTMRX-VKHMYHEASA-N |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Chlamydomonas reinhardtii
(NCBI:txid3055)
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See:
PubMed
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Saccharomyces cerevisiae
(NCBI:txid4932)
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Source: yeast.sf.net
See:
PubMed
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Escherichia coli
(NCBI:txid562)
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See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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See:
DOI
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Bronsted base
A molecular entity capable of accepting a hydron from a donor (Bronsted acid).
(via organic amino compound )
Bronsted acid
A molecular entity capable of donating a hydron to an acceptor (Bronsted base).
(via oxoacid )
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Escherichia coli metabolite
Any bacterial metabolite produced during a metabolic reaction in Escherichia coli.
Saccharomyces cerevisiae metabolite
Any fungal metabolite produced during a metabolic reaction in Baker's yeast (Saccharomyces cerevisiae ).
micronutrient
Any nutrient required in small quantities by organisms throughout their life in order to orchestrate a range of physiological functions.
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
EC 1.14.13.39 (nitric oxide synthase) inhibitor
An EC 1.14.13.* (oxidoreductase acting on paired donors, incorporating 1 atom of oxygen, with NADH or NADPH as one donor) inhibitor that interferes with the action of nitric oxide synthase (EC 1.14.13.39).
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
fundamental metabolite
Any metabolite produced by all living cells.
(via glutamine )
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nutraceutical
A product in capsule, tablet or liquid form that provide essential nutrients, such as a vitamin, an essential mineral, a protein, an herb, or similar nutritional substance.
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View more via ChEBI Ontology
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(2S)-2,5-diamino-5-oxopentanoic acid
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IUPAC
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(2S)-2-amino-4-carbamoylbutanoic acid
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JCBN
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(S)-2,5-diamino-5-oxopentanoic acid
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ChEBI
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Glutamic acid 5-amide
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HMDB
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Glutamic acid amide
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HMDB
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GLUTAMINE
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PDBeChem
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L-(+)-glutamine
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ChemIDplus
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L-2-Aminoglutaramic acid
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KEGG COMPOUND
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L-2-aminoglutaramic acid
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ChEBI
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L-2-aminoglutaramic acid
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DrugBank
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L-glutamic acid γ-amide
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NIST Chemistry WebBook
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L-Glutamin
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ChEBI
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L-Glutamine
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KEGG COMPOUND
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L-Glutaminsäure-5-amid
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ChEBI
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Levoglutamide
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KEGG DRUG
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Q
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ChEBI
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1311
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DrugCentral
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C00001359
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KNApSAcK
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C00064
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KEGG COMPOUND
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D00015
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KEGG DRUG
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DB00130
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DrugBank
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ECMDB00641
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ECMDB
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GLN
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MetaCyc
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GLN
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PDBeChem
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Glutamine
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Wikipedia
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HMDB0000641
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HMDB
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LSM-4741
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LINCS
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YMDB00002
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YMDB
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| View more database links |
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1723797
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Reaxys Registry Number
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Reaxys
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3509
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Gmelin Registry Number
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Gmelin
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56-85-9
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CAS Registry Number
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KEGG COMPOUND
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56-85-9
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CAS Registry Number
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NIST Chemistry WebBook
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56-85-9
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CAS Registry Number
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ChemIDplus
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Ostrov DA, Alkanani A, McDaniel KA, Case S, Baschal EE, Pyle L, Ellis S, Pöllinger B, Seidl KJ, Shah VN, Garg SK, Atkinson MA, Gottlieb PA, Michels AW (2018)
Methyldopa blocks MHC class II binding to disease-specific antigens in autoimmune diabetes.
The Journal of clinical investigation 128, 1888-1902 [PubMed:29438107]
[show Abstract]
Major histocompatibility (MHC) class II molecules are strongly associated with many autoimmune disorders. In type 1 diabetes (T1D), the DQ8 molecule is common, confers significant disease risk, and is involved in disease pathogenesis. We hypothesized that blocking DQ8 antigen presentation would provide therapeutic benefit by preventing recognition of self-peptides by pathogenic T cells. We used the crystal structure of DQ8 to select drug-like small molecules predicted to bind structural pockets in the MHC antigen-binding cleft. A limited number of the predicted compounds inhibited DQ8 antigen presentation in vitro, with 1 compound preventing insulin autoantibody production and delaying diabetes onset in an animal model of spontaneous autoimmune diabetes. An existing drug with a similar structure, methyldopa, specifically blocked DQ8 in patients with recent-onset T1D and reduced inflammatory T cell responses to insulin, highlighting the relevance of blocking disease-specific MHC class II antigen presentation to treat autoimmunity. | Dai ZL, Li XL, Xi PB, Zhang J, Wu G, Zhu WY (2013)
L-Glutamine regulates amino acid utilization by intestinal bacteria.
Amino acids 45, 501-512 [PubMed:22451274]
[show Abstract]
Catabolism of amino acids (AA) by intestinal bacteria greatly affects their bioavailability in the systemic circulation and the health of animals and humans. This study tests the novel hypothesis that L-glutamine regulates AA utilization by luminal bacteria of the small intestine. Pure bacterial strains (Streptococcus sp., Escherichia coli and Klebsiella sp.) and mixed bacterial cultures derived from the jejunum or ileum of pigs were cultured in the presence of 0-5 mM L-glutamine under anaerobic conditions. After 3 h of incubation, samples were taken for the determination of AA utilization. Results showed concentration-dependent increases in the utilization of glutamine in parallel with the increased conversion of glutamine into glutamate in all the bacteria. Complete utilization of asparagine, aspartate and serine was observed in pure bacterial strains after the 3-h incubation. The addition of glutamine reduced the net utilization of asparagine by both jejunal and ileal mixed bacteria. Net utilization of lysine, leucine, valine, ornithine and serine by jejunal or ileal mixed bacteria decreased with the addition of glutamine in a concentration-dependent manner. Collectively, glutamine dynamically modulates the bacterial metabolism of the arginine family of AA as well as the serine and aspartate families of AA and reduced the catabolism of most AA (including nutritionally essential and nonessential AA) in jejunal or ileal mixed bacteria. The beneficial effects of glutamine on gut nutrition and health may involve initiation of the signaling pathways related to AA metabolism in the luminal bacteria of the small intestine. | Roux A, Xu Y, Heilier JF, Olivier MF, Ezan E, Tabet JC, Junot C (2012)
Annotation of the human adult urinary metabolome and metabolite identification using ultra high performance liquid chromatography coupled to a linear quadrupole ion trap-Orbitrap mass spectrometer.
Analytical chemistry 84, 6429-6437 [PubMed:22770225]
[show Abstract]
Metabolic profiles of biofluids obtained by atmospheric pressure ionization mass spectrometry-based technologies contain hundreds to thousands of features, most of them remaining unknown or at least not characterized in analytical systems. We report here on the annotation of the human adult urinary metabolome and metabolite identification from electrospray ionization mass spectrometry (ESI-MS)-based metabolomics data sets. Features of biological interest were first of all annotated using the ESI-MS database of the laboratory. They were also grouped, thanks to software tools, and annotated using public databases. Metabolite identification was achieved using two complementary approaches: (i) formal identification by matching chromatographic retention times, mass spectra, and also product ion spectra (if required) of metabolites to be characterized in biological data sets to those of reference compounds and (ii) putative identification from biological data thanks to MS/MS experiments for metabolites not available in our chemical library. By these means, 384 metabolites corresponding to 1484 annotated features (659 in negative ion mode and 825 in positive ion mode) were characterized in human urine samples. Of these metabolites, 192 and 66 were formally and putatively identified, respectively, and 54 are reported in human urine for the first time. These lists of features could be used by other laboratories to annotate their ESI-MS metabolomics data sets. | Pistolesi S, Tjandra N (2012)
Temperature dependence of molecular interactions involved in defining stability of glutamine binding protein and its complex with L-glutamine.
Biochemistry 51, 643-652 [PubMed:22206385]
[show Abstract]
The temperature dependence of dynamic parameters derived from nuclear magnetic resonance (NMR) relaxation data is related to conformational entropy of the system under study. This provides information such as macromolecules stability and thermodynamics of ligand binding. We studied the temperature dependence of NMR order parameter of glutamine binding protein (GlnBP), a periplasmic binding protein (PBP) highly specific to L-glutamine associated with its ABC transporter, with the goal of elucidating the dynamical differences between the respective ligand bound and free forms. We found that the protein-ligand interaction, which is stabilized at higher temperature, has a striking effect on the stability of the hydrophobic core of the large domain of GlnBP. Moreover, in contrast to what was found for less specific PBPs, the decreasing backbone motion of the hinge region at increasing temperature supports the idea that the likelihood that GlnBP can adopt a ligand free closed conformation in solution diminishes at higher temperatures. Our results support the induced-fit model as mode of action for GlnBP. In addition, we found that the backbones of residues involved in a salt bridge do not necessarily become more rigid as the temperature rises as it was previously suggested [Vinther, J. M., et al. (2011) J. Am. Chem. Soc., 133, 271-278]. Our results show that for this to happen these residues have to also directly interact with a region of the protein that is becoming more rigid as the temperature increases. | Turkez H, Geyikoglu F, Yousef MI, Celik K, Bakir TO (2012)
Ameliorative effect of supplementation with L-glutamine on oxidative stress, DNA damage, cell viability and hepatotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat hepatocyte cultures.
Cytotechnology 64, 687-699 [PubMed:22453904]
[show Abstract]
The most potent of the dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is a persistent and ubiquitous environmental contaminant. And the health impact of exposure to TCDD is of great concern to the general public. Recent data indicate that L-glutamine (Gln) has antioxidant properties and may influence hepatotoxicity. The objective of the present study was undertaken to explore the effectiveness of Gln in alleviating the hepatotoxicity of TCDD on primary cultured rat hepatocytes. Gln (0.5, 1 and 2 mM) was added to cultures alone or simultaneously with TCDD (0.005 and 0.01 mM). The hepatocytes were treated with TCDD and Gln for 48 h. Then cell viability was detected by [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) assay and lactate dehydrogenase (LDH) release, while total antioxidant capacity (TAC), total glutathione (TGSH) and total oxidative stress (TOS) levels were determined to evaluate the oxidative injury. The DNA damage was also analyzed by liver micronucleus assay (MN) and 8-oxo-2-deoxyguanosine (8-OH-dG). The results of MTT and LDH assays showed that TCDD decreased cell viability but not L-glutamine. TCDD also increased TOS level in rat hepatocytes and significantly decreased TAC and TGSH levels. On the basis of increasing doses, the dioxin in a dose-dependent manner caused significant increases of micronucleated hepatocytes (MNHEPs) and 8-OH-dG as compared to control culture. Whereas, in cultures exposured with Gln alone, TOS levels were not changed and TAC and TGSH together were significantly increased in dose-dependent fashion. The presence of Gln with TCDD modulated the hepatotoxic effects of TCDD on primary hepatocytes cultures. Noteworthy, Gln has a protective effect against TCDD-mediated DNA damages. As conclusion, we reported here an increased potential therapeutic significance of L-glutamine in TCDD-mediated hepatic injury for the first time. | Cavalcante AA, Campelo MW, de Vasconcelos MP, Ferreira CM, Guimarães SB, Garcia JH, de Vasconcelos PR (2012)
Enteral nutrition supplemented with L-glutamine in patients with systemic inflammatory response syndrome due to pulmonary infection.
Nutrition (Burbank, Los Angeles County, Calif.) 28, 397-402 [PubMed:22055478]
[show Abstract]
ObjectiveTo evaluate the effect of enteral nutrition (EN) supplemented with l-glutamine on glycolytic parameters, inflammation, immune function, and oxidative stress in moderately ill intensive care patients with sepsis.MethodsThirty patients received EN. Fifteen patients received EN supplemented with glutamine (30 g; GLN group) for 2 d followed by EN supplemented with calcium caseinate (30 g, CAS group), also over 2 d. The other 15 patients received EN with calcium caseinate (30 g; CAS group) for 2 d followed by EN with glutamine (30 g; GLN group), also over 2 days. One washout day with only EN was provided between every 2-d period of EN plus supplementation to all patients. Blood samples were taken before and after supplementation.ResultsThere were no changes in glycolytic parameters in either group. Leukocytes decreased in the two groups (from 13 650 to 11 500 in the CAS group, P = 0.019; from 12.850 to 11.000 in the GLN group, P = 0.046). Lymphocytes increased in the GLN group (from 954 to 1916, P < 0.0001) and were more numerous after glutamine supplementation (from 1916 to 1085, P < 0.0001, GLN versus CAS). No significant changes were observed in interleukin levels, but urea levels were higher in the GLN compared with the CAS group (50.0-47.0, P = 0.030). Glutathione plasma concentrations did not differ significantly between the groups. No significant changes were observed in the plasma glutamine and glutamate concentrations.ConclusionsThe EN supplemented with glutamine increased the lymphocyte count and helped to decrease lipid peroxidation but presented no effect on the antioxidant glutathione capacity and on cytokine concentrations or glycolytic parameters. | Harris RC, Hoffman JR, Allsopp A, Routledge NB (2012)
L-glutamine absorption is enhanced after ingestion of L-alanylglutamine compared with the free amino acid or wheat protein.
Nutrition research (New York, N.Y.) 32, 272-277 [PubMed:22575040]
[show Abstract]
Differences in plasma L-glutamine (L-Gln) concentrations from ingestion of different formulations of L-Gln were examined in 8 men (26.8 ± 4.2 years old, 181.1 ± 10.9 cm, 85.8 ± 15.4 kg). Subjects reported to the laboratory on 4 separate occasions and randomly consumed 1 of 4 drinks containing 60 mg/kg of L-Gln; 89 mg/kg of Sustamine (L-alanylglutamine [AlaGln]; Kyowa Hakko Europe GmbH, Düsseldorf, Germany), which contained an equivalent L-Gln dose as consumed in L-Gln); 200 mg/kg of an enzymatically hydrolyzed wheat protein (HWP) with an L-Gln content of 31 mg/kg; or a control that consisted only of water. It was hypothesized that the AlaGln trial would increase plasma glutamine concentrations greater than the other experimental trials. Ingestion of L-Gln, AlaGln, and HWP resulted in significant increases in the plasma L-Gln concentration, peaking at 0.5, 0.5, and 0.75 hours, respectively. The corresponding mean peak increases were 179 ± 61, 284 ± 84, and 134 ± 36 μmol/L, respectively. Concentrations returned to baseline in all subjects by 2 hours after L-Gln and HWP and by 4 hours after AlaGln. Mean areas under the plasma concentration curve, calculated between 0 and 4 hours, were 127 ± 61, 284 ± 154, and 151 ± 63 μmol∙h∙L⁻¹ for L-Gln, AlaGln, and HWP, respectively. When allowance was made for the lower L-Gln dose administered as HWP, the peak plasma concentration and area under the plasma concentration curve were approximately the same as for AlaGln. The results suggest a greater transfer from the gut to plasma of L-Gln when supplied as AlaGln and possibly also as HWP compared with when the same dose was provided as the free amino acid. | Tsubuku S, Hatayama K, Mawatari K, Smriga M, Kimura T (2004)
Thirteen-week oral toxicity study of L-glutamine in rats.
International journal of toxicology 23, 107-112 [PubMed:15204730]
[show Abstract]
L-Glutamine (Gln) is a semiessential amino acid used in enteral feeding in critically ill patients, and is contained in numerous dietary supplements available to the general public. This study evaluated toxicological effects of Gln in male and female Sprague-Dawley rats. Gln produced by Ajinomoto Co. (Tokyo, Japan) was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% (w/w), respectively. A control group of rats received only a standard diet. All diets were administered ad libitum for 13 consecutive weeks. To examine recoverability of any potential effects, the administration period was followed by a 5-week recovery period, during which only the standard diet was provided to all animals. Throughout the administration and recovery periods, no deaths were observed, and no changes in diet consumption, ophthalmologic findings, gross pathology, and histopathology were detected. Several changes in urine parameters (total protein, urine pH, and a positive incidence (+/-) of ketone bodies) were observed in the 2.5% and 5.0% groups at the end of the administration period. Minor increases were found in hematology parameters for the 5.0% group (platelet count, gamma-globulin, lactate dehydrogenase [LDH]), but all changes were within physiological range. No effects of administration were observed in the 1.25% group. The no-observed-adverse-effect level (NOAEL) for Gln was estimated at 1.25% for both genders (males 0.83 +/- 0.01 g/kg/day; females, 0.96 +/- 0.06 g/kg/day). | Wu G, Haynes TE, Li H, Yan W, Meininger CJ (2001)
Glutamine metabolism to glucosamine is necessary for glutamine inhibition of endothelial nitric oxide synthesis.
The Biochemical journal 353, 245-252 [PubMed:11139387]
[show Abstract]
L-Glutamine is a physiological inhibitor of endothelial NO synthesis. The present study was conducted to test the hypothesis that metabolism of glutamine to glucosamine is necessary for glutamine inhibition of endothelial NO generation. Bovine venular endothelial cells were cultured for 24 h in the presence of 0, 0.1, 0.5 or 2 mM D-glucosamine, or of 0.2 or 2 mM L-glutamine with or without 20 microM 6-diazo-5-oxo-L-norleucine (DON) or with 100 microM azaserine. Both DON and azaserine are inhibitors of L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) (EC 2.6.1.16), the first and rate controlling enzyme in glucosamine synthesis. Glucosamine at 0.1, 0.5 and 2 mM decreased NO production by 34, 45 and 56% respectively compared with controls where glucosamine was lacking. DON (20 microM) and azaserine (100 microM) blocked glucosamine synthesis and prevented the inhibition of NO generation by glutamine. Neither glutamine nor glucosamine had an effect on NO synthase (NOS) activity, arginine transport or cellular tetrahydrobiopterin and Ca(2+) levels. However, both glutamine and glucosamine inhibited pentose cycle activity and decreased cellular NADPH concentrations; these effects of glutamine were abolished by DON or azaserine. Restoration of cellular NADPH levels by the addition of 1 mM citrate also prevented the inhibiting effect of glutamine or glucosamine on NO synthesis. A further increase in cellular NADPH levels by the addition of 5 mM citrate resulted in greater production of NO. Collectively, our results demonstrate that the metabolism of glutamine to glucosamine is necessary for the inhibition of endothelial NO generation by glutamine. Glucosamine reduces the cellular availability of NADPH (an essential cofactor for NOS) by inhibiting pentose cycle activity, and this may be a metabolic basis for the inhibition of endothelial NO synthesis by glucosamine. |
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