The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

glutamate     2-aminopentanedioic acid

Synonyms: Glutaminsaeure, DL-Glu, DL-Glutamate, H-DL-Glu-OH, GLUTAMIC ACID, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of glutamate

  • Stratification of patients into those with and without macroscopic emphysema (EMPH+, EMPH-, respectively), with comparable physical activity levels on the basis of previous observations, revealed lower values for La threshold and GLU in EMPH+ patients [1].
  • This study illustrates that the early lactic acidosis during exercise in patients with COPD is associated with the physical inactivity-related reduction in these patient's muscle GLU [1].
  • Carbon monoxide metabolism of the methylotrophic acidogen Butyribacterium methylotrophicum [2].
  • Dry/wet heart weight ratios were also greater in GGA (0.20), when compared with G2 (0.16), GX (0.17), GM (0.17), GM (0.17), and GL (0.17) (all p < 0.02), suggesting less cellular/interstitial edema [3].
  • Reperfusion arrhythmia (in sec) was significantly (all p < 0.05) shorter in GGA (115 +/- 33) vs G1 (315 +/- 29) and G2 (273 +/- 33), and also in GL (161 +/- 26) vs G1 [3].
  • Glutamate release from VMH neurons is an important component of the neurocircuitry that functions to prevent hypoglycemia [4].
  • Glioma cells release glutamate in sufficient quantities to activate AMPA-Rs on themselves or neighboring cells, thus acting in an autocrine and/or paracrine fashion [5].
  • Cerebral ischemia is associated with an excessive release of glutamate, and in postischemic cerebral edema ablation of AQP4 attenuates the degree of damage [6].
  • Glutamate deprivation or blockade decreased prostate cancer cells' proliferation, migration, and invasion and led to apoptotic cell death [7].

Psychiatry related information on glutamate

  • BOD estimations for the GGA standard resulted in an extended linear range: 2-100 mg/l. Response reproducibility was +/-10% for a GGA standard containing 10 mg BOD/l. For analysis of pulp mill effluents, the BOD detection limit was 2 mg/l with a response time of 5 min [8].
  • These data suggest that glutamate receptor expression is altered in the medial temporal lobe in schizophrenia and the mood disorders [9].
  • This study suggests that glutamate plays a role in the pathophysiology of bipolar disorder and major depression [10].

High impact information on glutamate

  • At the molecular level, LTD appears to be caused by desensitization of receptor molecules in PC dendrites towards the PF neurotransmitter, presumably L-glutamate (Glu) [11].
  • Decreases in the current threshold for locomotion produced by electrical stimulation of the MRF were observed when the MRF was infused with either GA (40-80 nmol), DL-homocysteic acid (DL-HCA; 200 nmol), or picrotoxin (PIC; 15 nmol) [12].
  • The COPD group had lower values for La threshold and muscle GLU, and higher values for muscle La and pyruvate levels than did the PI group [1].
  • The minor alternative transcript skips both exon 2 and exon 3 (FVII Delta 2, 3), leading to an in-frame deletion of the propeptide and gamma-carboxylated glutamic acid (Gla) domains of mature FVII protein [13].
  • In the vertebrate CNS, Gly acts both as an inhibitory neurotransmitter and as a Glu modulator or coagonist at postsynaptic N-methyl-D-aspartate (NMDA) receptors [14].

Chemical compound and disease context of glutamate


Biological context of glutamate

  • The maximal extent of inhibition (1 mM) was both amino acid-dependent (IC50: NMDA, 5 microM; KA, 3.3 microM; QUIS, 47 microM; GLU, greater than 1 mM) [17].
  • The pretreatment of BT-11 (0.5, 3, and 5 micro g/ml) significantly reduced cell death induced by Glu (1 mM), A beta (10 micro M) and CT105 (10 micro M) in a dose-dependent manner [18].
  • Cell survival was reduced to 31% in GLU-treated neuronal cultures; PKC inhibitors were not able to modify this effect [19].
  • The application of Ka (1 x 10(-8) to 1 x 10(-6) M), NMDA (1 x 10(-8) to 1 x 10(-4) M), Quis (1 x 10(-7) to 1 x 10(-4) M), Glu (1 x 10(-5) to 5 x 10(-4) M), and Asp (1 x 10(-5) to 5 x 10(-3) M) enhanced the oxygen consumption dose-dependently, to a maximum of 120-146% of the resting level (8.43 mumol/g protein/min) [20].
  • These results support the proposal that the D-aspartate-insensitive Glu binding site is somehow related to an amino acid receptor-mediated modulation of dopaminergic transmission in the rat corpus striatum [21].

Anatomical context of glutamate


Associations of glutamate with other chemical compounds

  • A colocalization of Gly transporters and NMDA receptors has been reported in brain tissue (Smith et al. Neuron 8:927-936, 1992); since the concentration of Gly could participate in the modulation of Glu excitatory transmission in the vertical pathways of the retina, transport of Gly in monolayer cultures of Müller cells was studied [14].
  • Homo-AMPA (8), which is a 3-isoxazolol bioisostere of 2-aminoadipic acid (3), was, however, shown to be a specific and rather potent agonist at mGlu6, approximately 4 times weaker than the nonselective excitatory amino acid receptor agonist (S)-glutamic acid [27].
  • Endogenous GLU release from OGD slices increased to about 15 times the basal values after 15 min of oxygen-glucose deprivation, and to 25 and 35 times the basal level in the presence of the PKC inhibitors staurosporine (0.1 microM) and bisindolylmaleimide (1 microM), respectively [19].
  • Using the high-affinity mutant (E363D) of bovine retinal CNG channel in which the Glu at position 363 was replaced to Asp, we constructed tandem dimers and investigated the binding characteristics of divalent cations to the site [28].
  • This regulatory mechanism by the bifunctional enzyme RocG allows the tight control of glutamate metabolism by the availability of carbon and nitrogen sources [29].
  • Treating cells with EGTA-AM plus wortmannin essentially abolished Thr-dependent glutamate efflux [30].
  • Either Nedd4 or PTEN knockdown with small interfering RNA prevented the morphine-induced EAAC1 degradation and decreased glutamate uptake [31].
  • Moreover pinacidil, diazoxide, and iptakalim reversed the inhibition of glutamate uptake induced by 1-methyl-4-phenylpyridinium (MPP+) [32].
  • Glutamate activation of N-methyl-D-aspartate (NMDA) receptors in the MPOA is at least partly responsible for behavioral effects evoked by increase glutamate [33].
  • This conformation is stabilized by contacts between large hydrophobic patches in the R2 domain that are absent in NMDA receptors, suggesting that the ATDs of individual glutamate receptor ion channels have evolved into functionally distinct families [34].
  • With the non-bovine serum albumin brain and heart mitochondria oxidizing succinate, the addition of pyruvate and glutamate abrogated inhibition of Complex II by oxaloacetate [35].

Gene context of glutamate

  • Added Glu resulted in significantly increased TNF-alpha levels in primary synovial cell cultures [24].
  • The data indicate that substitution for Glu in an antifolate by some Glu analogs in which the gamma-COOH is either altered or replaced (e.g., gamma-tetrazole-Glu) leads to loss of both FPGS substrate activity and binding; antifolate target specificity is unchanged, while uptake is actually enhanced [36].
  • Percent recovery in PLVP was improved (p < 0.03) in GL (81 +/- 2) and GGA (81 +/- 2) vs. G2 (71 +/- 3), without significant alterations in oxygen consumption [3].
  • Microinjection of 4-10 nl of 0.18 M Glu in 30 of 39 explored sites at the T2 level elicited significant increases in HR (+24.2 +/- 3.1 beats/min) [37].
  • These findings demonstrate that the cell response to OGD and GLU involves PKC in a complex way [19].
  • All these data show that the GLT1/EAAT2 glutamate transporter is a target gene of PPARgamma leading to neuroprotection by increasing glutamate uptake [38].
  • We show that mice deficient in the glutamate transporters GLAST or EAAC1 demonstrate spontaneous RGC and optic nerve degeneration without elevated IOP [39].
  • Inhibition of N-methyl-D-aspartate (NMDA) receptors in RA FLS increased proMMP-2 release, whereas non-NMDA ionotropic glutamate receptor antagonists reduced IL-6 production by these cells [40].

Analytical, diagnostic and therapeutic context of glutamate

  • Western blot analysis of GLU-treated cortical neurons showed a significant decrease only in the total level of beta(2) isoforms [19].
  • In the rest of microinjections Gly and Glu produced changes of SAP and VNA in different combinations [41].
  • The adsorption of the amino acid, (S)-glutamic acid, was investigated on Ag{110} as a function of coverage and adsorption temperature using the techniques of scanning tunneling microscopy, low energy electron diffraction, and reflection absorption infrared spectroscopy [42].


  1. Exercise-induced lactate increase in relation to muscle substrates in patients with chronic obstructive pulmonary disease. Engelen, M.P., Schols, A.M., Does, J.D., Gosker, H.R., Deutz, N.E., Wouters, E.F. Am. J. Respir. Crit. Care Med. (2000) [Pubmed]
  2. Carbon monoxide metabolism of the methylotrophic acidogen Butyribacterium methylotrophicum. Lynd, L., Kerby, R., Zeikus, J.G. J. Bacteriol. (1982) [Pubmed]
  3. Effect of substrate manipulation on reducing ischemia/reperfusion injury in isolated perfused rat hearts. Wiese, S., Askanazi, J., Manner, T., Katz, D.P., Buttrick, P. Clinical nutrition (Edinburgh, Scotland) (1995) [Pubmed]
  4. Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemia. Tong, Q., Ye, C., McCrimmon, R.J., Dhillon, H., Choi, B., Kramer, M.D., Yu, J., Yang, Z., Christiansen, L.M., Lee, C.E., Choi, C.S., Zigman, J.M., Shulman, G.I., Sherwin, R.S., Elmquist, J.K., Lowell, B.B. Cell Metab. (2007) [Pubmed]
  5. Autocrine glutamate signaling promotes glioma cell invasion. Lyons, S.A., Chung, W.J., Weaver, A.K., Ogunrinu, T., Sontheimer, H. Cancer Res. (2007) [Pubmed]
  6. Identification of a molecular target for glutamate regulation of astrocyte water permeability. Gunnarson, E., Zelenina, M., Axehult, G., Song, Y., Bondar, A., Krieger, P., Brismar, H., Zelenin, S., Aperia, A. Glia (2008) [Pubmed]
  7. Serum glutamate levels correlate with Gleason score and glutamate blockade decreases proliferation, migration, and invasion and induces apoptosis in prostate cancer cells. Koochekpour, S., Majumdar, S., Azabdaftari, G., Attwood, K., Scioneaux, R., Subramani, D., Manhardt, C., Lorusso, G.D., Willard, S.S., Thompson, H., Shourideh, M., Rezaei, K., Sartor, O., Mohler, J.L., Vessella, R.L. Clin. Cancer Res. (2012) [Pubmed]
  8. Mediated microbial biosensor using a novel yeast strain for wastewater BOD measurement. Trosok, S.P., Driscoll, B.T., Luong, J.H. Appl. Microbiol. Biotechnol. (2001) [Pubmed]
  9. Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Beneyto, M., Kristiansen, L.V., Oni-Orisan, A., McCullumsmith, R.E., Meador-Woodruff, J.H. Neuropsychopharmacology (2007) [Pubmed]
  10. Increased levels of glutamate in brains from patients with mood disorders. Hashimoto, K., Sawa, A., Iyo, M. Biol. Psychiatry (2007) [Pubmed]
  11. Quisqualate receptors are specifically involved in cerebellar synaptic plasticity. Kano, M., Kato, M. Nature (1987) [Pubmed]
  12. Locomotion produced in mesencephalic cats by injections of putative transmitter substances and antagonists into the medial reticular formation and the pontomedullary locomotor strip. Noga, B.R., Kettler, J., Jordan, L.M. J. Neurosci. (1988) [Pubmed]
  13. Novel aberrant splicings caused by a splice site mutation (IVS1a+5g>a) in F7 gene. Ding, Q., Wu, W., Fu, Q., Wang, X., Hu, Y., Wang, H., Wang, Z. Thromb. Haemost. (2005) [Pubmed]
  14. Characterization of glycine transport in cultured Müller glial cells from the retina. Gadea, A., López, E., López-Colomé, A.M. Glia (1999) [Pubmed]
  15. Stereochemical course of the decarboxylation of (S)-glutamic acid by glutamate decarboxylase from Escherichia coli (E.C. Santaniello, E., Kienle, M.G., Manzocchi, A., Bosisio, E. J. Chem. Soc. Perkin Trans. I (1979) [Pubmed]
  16. Application of microdialysis technique in the traditional chinese medicine. Zhang, S., Zeng, X., Xu, X., Zheng, X. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference (2005) [Pubmed]
  17. Excitatory amino acids modulate phosphoinositide signal transduction in human epileptic neocortex. Dubeau, F., Sherwin, A., Olivier, A., Villemure, J., Leblanc, R., Quesney, L.F., Andermann, E., Andermann, F. Epilepsia (1992) [Pubmed]
  18. Novel cognitive improving and neuroprotective activities of Polygala tenuifolia Willdenow extract, BT-11. Park, C.H., Choi, S.H., Koo, J.W., Seo, J.H., Kim, H.S., Jeong, S.J., Suh, Y.H. J. Neurosci. Res. (2002) [Pubmed]
  19. Protein kinase C activity, translocation, and selective isoform subcellular redistribution in the rat cerebral cortex after in vitro ischemia. Selvatici, R., Marino, S., Piubello, C., Rodi, D., Beani, L., Gandini, E., Siniscalchi, A. J. Neurosci. Res. (2003) [Pubmed]
  20. Effects of excitatory amino acids on the oxygen consumption of hippocampal slices from the guinea pig. Nishizaki, T., Okada, Y. Brain Res. (1988) [Pubmed]
  21. Functional and biochemical characteristics of a putative quisqualate-type receptor in rat striatum: effect of brain lesions. Rudolph, M.I., Bustos, G. Neurochem. Res. (1986) [Pubmed]
  22. The AMPA receptor binding site: focus on agonists and competitive antagonists. Stensbøl, T.B., Madsen, U., Krogsgaard-Larsen, P. Curr. Pharm. Des. (2002) [Pubmed]
  23. Effects of puerarin on learning-memory and amino acid transmitters of brain in ovariectomized mice. Xu, X., Hu, Y., Ruan, Q. Planta Med. (2004) [Pubmed]
  24. Excitatory amino acids, TNF-alpha, and chemokine levels in synovial fluids of patients with active arthropathies. McNearney, T., Baethge, B.A., Cao, S., Alam, R., Lisse, J.R., Westlund, K.N. Clin. Exp. Immunol. (2004) [Pubmed]
  25. Tryptophan inhibits the [3H]glutamate uptake into Xenopus oocytes injected with rat brain mRNA. Tohda, M., Urushihara, H., Nomura, Y. Jpn. J. Pharmacol. (1992) [Pubmed]
  26. Neurotoxicity of diethylpropion: neurochemical and behavioral findings in rats. Galvan-Arzate, S., Santamaria, A. Ann. N. Y. Acad. Sci. (2002) [Pubmed]
  27. A new highly selective metabotropic excitatory amino acid agonist: 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid. Bräuner-Osborne, H., Sløk, F.A., Skjaerbaek, N., Ebert, B., Sekiyama, N., Nakanishi, S., Krogsgaard-Larsen, P. J. Med. Chem. (1996) [Pubmed]
  28. Binding symmetry of extracellular divalent cations to conduction pore studied using tandem dimers of a CNG channel. Kwon, R.J., Ha, T.S., Kim, W., Park, C.S. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  29. A regulatory protein-protein interaction governs glutamate biosynthesis in Bacillus subtilis: the glutamate dehydrogenase RocG moonlights in controlling the transcription factor GltC. Commichau, F.M., Herzberg, C., Tripal, P., Valerius, O., Stülke, J. Mol. Microbiol. (2007) [Pubmed]
  30. Thrombin potently enhances swelling-sensitive glutamate efflux from cultured astrocytes. Ramos-Mandujano, G., Vázquez-Juárez, E., Hernández-Benítez, R., Pasantes-Morales, H. Glia (2007) [Pubmed]
  31. Morphine induces ubiquitin-proteasome activity and glutamate transporter degradation. Yang, L., Wang, S., Sung, B., Lim, G., Mao, J. J. Biol. Chem. (2008) [Pubmed]
  32. KATP channel openers facilitate glutamate uptake by GluTs in rat primary cultured astrocytes. Sun, X.L., Zeng, X.N., Zhou, F., Dai, C.P., Ding, J.H., Hu, G. Neuropsychopharmacology (2008) [Pubmed]
  33. A role for preoptic glutamate in the regulation of male reproductive behavior. Dominguez, J.M. Neuroscientist (2009) [Pubmed]
  34. The N-terminal domain of GluR6-subtype glutamate receptor ion channels. Kumar, J., Schuck, P., Jin, R., Mayer, M.L. Nat. Struct. Mol. Biol. (2009) [Pubmed]
  35. The neuromediator glutamate, through specific substrate interactions, enhances mitochondrial ATP production and reactive oxygen species generation in nonsynaptic brain mitochondria. Panov, A., Schonfeld, P., Dikalov, S., Hemendinger, R., Bonkovsky, H.L., Brooks, B.R. J. Biol. Chem. (2009) [Pubmed]
  36. Exploitation of folate and antifolate polyglutamylation to achieve selective anticancer chemotherapy. McGuire, J.J., Tsukamoto, T., Hart, B.P., Coward, J.K., Kalman, T.I., Galivan, J. Investigational new drugs. (1996) [Pubmed]
  37. Microinjection of substance P and ACh into rat intermediolateral nucleus elicits cardiovascular responses. Calaresu, F.R., McKitrick, D.J., Weernink, E.J. Am. J. Physiol. (1990) [Pubmed]
  38. Ischemic preconditioning reveals that GLT1/EAAT2 glutamate transporter is a novel PPARgamma target gene involved in neuroprotection. Romera, C., Hurtado, O., Mallolas, J., Pereira, M.P., Morales, J.R., Romera, A., Serena, J., Vivancos, J., Nombela, F., Lorenzo, P., Lizasoain, I., Moro, M.A. J. Cereb. Blood Flow Metab. (2007) [Pubmed]
  39. The potential role of glutamate transporters in the pathogenesis of normal tension glaucoma. Harada, T., Harada, C., Nakamura, K., Quah, H.M., Okumura, A., Namekata, K., Saeki, T., Aihara, M., Yoshida, H., Mitani, A., Tanaka, K. J. Clin. Invest. (2007) [Pubmed]
  40. Modulation of interleukin-6 and matrix metalloproteinase 2 expression in human fibroblast-like synoviocytes by functional ionotropic glutamate receptors. Flood, S., Parri, R., Williams, A., Duance, V., Mason, D. Arthritis Rheum. (2007) [Pubmed]
  41. Glycine produced pressor responses when microinjected in the pressor areas of pons and medulla in cats. Wu, W.C., Chen, S.Y., Kuo, J.S., Chai, C.Y. J. Auton. Nerv. Syst. (1996) [Pubmed]
  42. Molecular ordering and adsorbate induced faceting in the Ag{110}-(S)-glutamic acid system. Jones, T.E., Baddeley, C.J., Gerbi, A., Savio, L., Rocca, M., Vattuone, L. Langmuir : the ACS journal of surfaces and colloids. (2005) [Pubmed]
WikiGenes - Universities