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Chemical Compound Review

glutamate     2-azaniumylpentanedioate

Synonyms: glutamate(1-), AC1NBYR0, CHEBI:14321, hydrogen glutamate, Glutamine Analogue, 4, ...
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High impact information on glutamate

  • Dorsal periaqueductal gray (dPAG) neurons express NMDA/GLY(B) receptors suggesting a GLU physiological role in mediating the responses elicited by stimulation of this area [1].
  • The intracellular pool of Glu and Asp was also reduced in kainate-lesioned striata [2].
  • Our data thus suggest that neither SNAT1 nor SNAT2 meet the criteria for their postulated role in the "glutamate-glutamine" cycle, and indicate that other Gln transporters (either orphan or yet to be identified) must be expressed at axon terminals and sustain the Glu (and gamma-aminobutyric acid) neurotransmitter pool (s) [3].
  • This study explored functional interactions between DA and glutamate (Glu) systems using the NMDA receptor antagonist MK-801 and the DA receptor agonists 7-OH-DPAT and apomorphine [4].
  • Double-labeling studies revealed that of the c-Fos-positive neurons responsive to hypertonic NaCl, 52%, 41%, and 3% exhibited immunoreactivity for Glu, SP, and CGRP, respectively [5].

Biological context of glutamate

  • We previously showed that Gln potently inhibited apoptosis in cytokine-treated human colonic HT-29 cells; this effect was specific to Gln, unaffected by Glu, and unrelated to intracellular GSH [6].
  • We have used site-directed in vitro mutagenesis to replace the His codon of the esterase 6 gene with either Gln or Glu codons [7].

Anatomical context of glutamate

  • These results suggest that in the nucleus accumbens, ASP and GLU may increase dopamine release through distinct mechanisms and that their stimulatory action is dependent on axonal impulse flow [8].
  • However, His significantly decreased to almost the preincubation level the content of Glu in mitochondria incubated with Gln, without affecting the content of Gln [9].
  • We also measured the ex vivo tissue level of glutamate (Glu), dopamine (DA) and serotonin (5-HT) as well as the DA metabolites DOPAC and the major 5-HT metabolite HIAA to determine the neurochemical effects of ketamine (12 mg/kg) and LY379268 (1 mg/kg) in the dentate gyrus (DG) [10].
  • Glu released from neurons is taken up by astrocytes, and reconverted to Gln, closing the so called "glutamate-glutamine" cycle [11].
  • Methionine S-sulfoximine, an inhibitor of Gln synthetase, did not reverse the inhibitory effect of Glu of PEP formation from malate in chicken liver mitochondria [12].

Associations of glutamate with other chemical compounds

  • Microinjection of sodium glutamate (Glu, 0.25 M, 30 nl) or Gly (1.0 M, 30 nl) into the DM or RVLM increased SAP and VNA in similar magnitude [13].
  • Cells treated with Glu, glucosamine, arginine, or nucleotide monophosphate mixture showed a decrease in proliferation compared with cells treated with Gln across all treatment doses (P < 0.03) [14].
  • METHODS: Glu with added ammonia acetate, glucosamine, arginine, and nucleotide monophosphates were tested at concentrations that were isonitrogenous with respect to Gln [14].
  • Glutamate + malate (glu/mal) supported respiration was diminished only in mitochondria isolated from brain stem of 2,5-HD treated rats [15].
  • While Gln and Glu required 24 h for maximal stimulation of prolidase activity, P5C induced it after 6-12 h [16].

Gene context of glutamate

  • Gln but not Glu decreased plasma CINC peptide (P < 0.05) [17].
  • Intestinal and plasma TNF-alpha were increased in GF, LPS-treated pups (P < 0.01), and Gln and Glu both blunted this increase (P < 0.05) in the intestine but not in the plasma [17].
  • Substitution of Gln for His at position 187 has little effect on the biochemical properties of esterase 6, but the presence of Glu at this position is associated with three major differences [7].
  • This demand is met by intracerebral Gln synthesis from glutamate (Glu), a reaction carried out by glutamine synthetase (GS), an enzyme residing in astrocytes [11].

Analytical, diagnostic and therapeutic context of glutamate

  • Perfusion of tetrodotoxin before application of either GLU or ASP blocked the excitatory effect of these amino acids on dopamine overflow [8].
  • Subsequently, the mitochondrial contents of Glu and Gln were determined by HPLC [9].


  1. Modulation of defensive behavior by periaqueductal gray NMDA/glycine-B receptor. Carobrez, A.P., Teixeira, K.V., Graeff, F.G. Neuroscience and biobehavioral reviews. (2001) [Pubmed]
  2. In vivo studies on the extracellular, and veratrine-releasable, pools of endogenous amino acids in the rat striatum: effects of corticostriatal deafferentation and kainic acid lesion. Butcher, S.P., Hamberger, A. J. Neurochem. (1987) [Pubmed]
  3. The glutamine commute: lost in the tube? Conti, F., Melone, M. Neurochem. Int. (2006) [Pubmed]
  4. Differential effects of 7-OH-DPAT and apomorphine on hyperactivity induced by MK-801 (dizocilpine) in rats. Clements, R.L., Greenshaw, A.J. Neuropharmacology (2005) [Pubmed]
  5. Neurochemical phenotype of vagal afferent neurons activated to express C-FOS in response to luminal stimulation in the rat. Wu, X.Y., Zhu, J.X., Gao, J., Owyang, C., Li, Y. Neuroscience (2005) [Pubmed]
  6. Glutamine inhibits cytokine-induced apoptosis in human colonic epithelial cells via the pyrimidine pathway. Evans, M.E., Jones, D.P., Ziegler, T.R. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  7. Effects of the residue adjacent to the reactive serine on the substrate interactions of Drosophila esterase 6. Myers, M.A., Healy, M.J., Oakeshott, J.G. Biochem. Genet. (1993) [Pubmed]
  8. Distinct actions of endogenous excitatory amino acids on the outflow of dopamine in the nucleus accumbens. Youngren, K.D., Daly, D.A., Moghaddam, B. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
  9. Analysis of glutamine accumulation in rat brain mitochondria in the presence of a glutamine uptake inhibitor, histidine, reveals glutamine pools with a distinct access to deamidation. Ziemińska, E., Hilgier, W., Waagepetersen, H.S., Hertz, L., Sonnewald, U., Schousboe, A., Albrecht, J. Neurochem. Res. (2004) [Pubmed]
  10. Effects of the mGluR2/3 agonist LY379268 on ketamine-evoked behaviours and neurochemical changes in the dentate gyrus of the rat. Imre, G., Salomons, A., Jongsma, M., Fokkema, D.S., Den Boer, J.A., Ter Horst, G.J. Pharmacol. Biochem. Behav. (2006) [Pubmed]
  11. Glutamine in the central nervous system: function and dysfunction. Albrecht, J., Sonnewald, U., Waagepetersen, H.S., Schousboe, A. Front. Biosci. (2007) [Pubmed]
  12. Relationships between phosphoenolpyruvate synthesis and glutamine formation in isolated chicken liver mitochondria. Deaciuc, I.V., Papadakis, M. Comp. Biochem. Physiol., B (1984) [Pubmed]
  13. Glycine increases arterial pressure and augments NMDA-induced pressor responses in the dorsomedial and ventrolateral medulla of cats. Wu, W.C., Kuo, J.S., Wang, Y., Chai, C.Y. J. Auton. Nerv. Syst. (1997) [Pubmed]
  14. Substitutes for glutamine in proliferation of rat intestinal epithelial cells. Tuhacek, L.M., Mackey, A.D., Li, N., DeMarco, V.G., Stevens, G., Neu, J. Nutrition (Burbank, Los Angeles County, Calif.) (2004) [Pubmed]
  15. Effects of acrylamide and 2,5-hexanedione on brain mitochondrial respiration. Medrano, C.J., LoPachin, R.M. Neurotoxicology (1989) [Pubmed]
  16. The potential mechanism for glutamine-induced collagen biosynthesis in cultured human skin fibroblasts. Karna, E., Miltyk, W., Wołczyński, S., Pałka, J.A. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. (2001) [Pubmed]
  17. Glutamine decreases lipopolysaccharide-induced intestinal inflammation in infant rats. Li, N., Liboni, K., Fang, M.Z., Samuelson, D., Lewis, P., Patel, R., Neu, J. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
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