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Chemical Compound Review

glutamate     2-aminopentanedioate

Synonyms: glutamate(2-), AC1NNVU2, CHEBI:29987, CTK9A3972, 2094-EP2269977A2, ...
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Disease relevance of glutamate


Psychiatry related information on glutamate

  • We measured high-affinity, sodium-dependent glutamate transport in synaptosomes from neural tissue obtained from 13 patients with ALS, 17 patients with no neurologic disease, and 27 patients with other neuro-degenerative diseases (Alzheimer's disease in 15 patients and Huntington's disease in 12 patients) [3].
  • Glutamate neurotoxicity and Huntington's chorea [5].
  • We report here that the selective disruption of postsynaptic activation in rat S1 by application of a glutamate receptor antagonist inhibits rearrangements in the somatotopic patterning of thalamocortical afferents induced by manipulations of the sensory periphery during the critical period [6].
  • This drug reduced augmented glutamate levels and normalized increased alcohol consumption in Per2(Brdm1) mutant mice [7].
  • Metabotropic glutamate (mGlu) receptors, which are responsible for slow glutamate-mediated neurotransmission, are located throughout limbic and cortical brain regions that are implicated in drug addiction [8].

High impact information on glutamate

  • Now that we appreciate this range of actions of astrocytic signaling, some of the immediate challenges are to determine how the astrocyte regulates neuronal integration and how both excitatory (glutamate) and inhibitory signals (adenosine) provided by the same glial cell act in concert to regulate neuronal function [9].
  • Astrocyte-derived glutamate, which preferentially acts on extrasynaptic receptors, can promote neuronal synchrony, enhance neuronal excitability, and modulate synaptic transmission [9].
  • Section IV covers second messengers, protein kinases, phosphatases and other elements, eventually leading to inactivation of DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolone-propionate-selective glutamate receptors that mediate granule cell-to-Purkinje cell transmission [10].
  • Beta-III spectrin is highly expressed in Purkinje cells and has been shown to stabilize the glutamate transporter EAAT4 at the surface of the plasma membrane [11].
  • Spectrin mutations are a previously unknown cause of ataxia and neurodegenerative disease that affect membrane proteins involved in glutamate signaling [11].

Chemical compound and disease context of glutamate


Biological context of glutamate

  • Excitotoxicity is a process in which glutamate or other excitatory amino acids induce neuronal cell death [17].
  • Extensive studies have shown that long-term potentiation (LTP) of the excitatory postsynaptic current (EPSC) through glutamate receptors is induced by activation of N-methyl-D-asparate receptor (NMDA-R)--the coincidence detector--and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) [18].
  • Conversely, down-regulation of NCX by siRNA compromised neuronal Ca2+ handling, transforming the Ca2+ transient elicited by non-excitotoxic glutamate concentrations into a lethal Ca2+overload [19].
  • Here, we report the phenotype of mice with a single point mutation, glutamate 613 to arginine, that inactivates the inhibitory wedge of CD45 [20].
  • RNA editing in brain controls a determinant of ion flow in glutamate-gated channels [21].

Anatomical context of glutamate


Associations of glutamate with other chemical compounds


Gene context of glutamate

  • The enzyme glutamate dehydrogenase (GDH) is important for recycling the chief excitatory neurotransmitter, glutamate, during neurotransmission [31].
  • The NMDA (N-methyl-D-aspartate) subclass of glutamate receptor is essential for the synaptic plasticity thought to underlie learning and memory and for synaptic refinement during development [32].
  • We found that BDNF and neurotrophin-4/5 depolarized neurons just as rapidly as the neurotransmitter glutamate, even at a more than thousand-fold lower concentration [33].
  • Control of dynamic CFTR selectivity by glutamate and ATP in epithelial cells [34].
  • Collectively, these data establish glutamate as a link between dysfunction of the circadian clock gene Per2 and enhanced alcohol intake [7].

Analytical, diagnostic and therapeutic context of glutamate

  • First visualization of glutamate and GABA in neurones by immunocytochemistry [35].
  • Additionally, since some of these effects appear to be irreversible, we propose that the regulation of glutamate binding by cations might account for the extremely long-lasting potentiation of synaptic responses found in the hippocampus following bursts of repetitive electrical stimulation (see ref. 9 for a review) [36].
  • By analysing the responses of mouse central neurones to glutamate using the patch-clamp technique, we have now found a link between voltage sensitivity and Mg2+ sensitivity [37].
  • Detection of these changes in occupancy is made possible as the transducers are methylated at multiple glutamate residues such that their level of methylation reflects the most recent chemoeffector concentration [38].
  • We analysed the lateral mobility of native AMPA receptors containing the glutamate receptor subunit GluR2 in rat cultured hippocampal neurons, using single-particle tracking and video microscopy [39].


  1. Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Xiong, Z.G., Zhu, X.M., Chu, X.P., Minami, M., Hey, J., Wei, W.L., MacDonald, J.F., Wemmie, J.A., Price, M.P., Welsh, M.J., Simon, R.P. Cell (2004) [Pubmed]
  2. The enemy at the gates. Ca2+ entry through TRPM7 channels and anoxic neuronal death. Nicotera, P., Bano, D. Cell (2003) [Pubmed]
  3. Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. Rothstein, J.D., Martin, L.J., Kuncl, R.W. N. Engl. J. Med. (1992) [Pubmed]
  4. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. Stanley, C.A., Lieu, Y.K., Hsu, B.Y., Burlina, A.B., Greenberg, C.R., Hopwood, N.J., Perlman, K., Rich, B.H., Zammarchi, E., Poncz, M. N. Engl. J. Med. (1998) [Pubmed]
  5. Glutamate neurotoxicity and Huntington's chorea. Olney, J.W., de Gubareff, T. Nature (1978) [Pubmed]
  6. Postsynaptic control of plasticity in developing somatosensory cortex. Schlaggar, B.L., Fox, K., O'Leary, D.D. Nature (1993) [Pubmed]
  7. The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption. Spanagel, R., Pendyala, G., Abarca, C., Zghoul, T., Sanchis-Segura, C., Magnone, M.C., Lascorz, J., Depner, M., Holzberg, D., Soyka, M., Schreiber, S., Matsuda, F., Lathrop, M., Schumann, G., Albrecht, U. Nat. Med. (2005) [Pubmed]
  8. The ups and downs of addiction: role of metabotropic glutamate receptors. Kenny, P.J., Markou, A. Trends Pharmacol. Sci. (2004) [Pubmed]
  9. Astrocyte control of synaptic transmission and neurovascular coupling. Haydon, P.G., Carmignoto, G. Physiol. Rev. (2006) [Pubmed]
  10. Cerebellar long-term depression: characterization, signal transduction, and functional roles. Ito, M. Physiol. Rev. (2001) [Pubmed]
  11. Spectrin mutations cause spinocerebellar ataxia type 5. Ikeda, Y., Dick, K.A., Weatherspoon, M.R., Gincel, D., Armbrust, K.R., Dalton, J.C., Stevanin, G., Dürr, A., Zühlke, C., Bürk, K., Clark, H.B., Brice, A., Rothstein, J.D., Schut, L.J., Day, J.W., Ranum, L.P. Nat. Genet. (2006) [Pubmed]
  12. Pertussis toxin reverses adenosine inhibition of neuronal glutamate release. Dolphin, A.C., Prestwich, S.A. Nature (1985) [Pubmed]
  13. Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake. Szatkowski, M., Barbour, B., Attwell, D. Nature (1990) [Pubmed]
  14. The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Faden, A.I., Demediuk, P., Panter, S.S., Vink, R. Science (1989) [Pubmed]
  15. Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. Malmberg, A.B., Yaksh, T.L. Science (1992) [Pubmed]
  16. Striatal dopamine- and glutamate-mediated dysregulation in experimental parkinsonism. Chase, T.N., Oh, J.D. Trends Neurosci. (2000) [Pubmed]
  17. c-fos regulates neuronal excitability and survival. Zhang, J., Zhang, D., McQuade, J.S., Behbehani, M., Tsien, J.Z., Xu, M. Nat. Genet. (2002) [Pubmed]
  18. Common molecular pathways mediate long-term potentiation of synaptic excitation and slow synaptic inhibition. Huang, C.S., Shi, S.H., Ule, J., Ruggiu, M., Barker, L.A., Darnell, R.B., Jan, Y.N., Jan, L.Y. Cell (2005) [Pubmed]
  19. Cleavage of the plasma membrane Na+/Ca2+ exchanger in excitotoxicity. Bano, D., Young, K.W., Guerin, C.J., Lefeuvre, R., Rothwell, N.J., Naldini, L., Rizzuto, R., Carafoli, E., Nicotera, P. Cell (2005) [Pubmed]
  20. An inactivating point mutation in the inhibitory wedge of CD45 causes lymphoproliferation and autoimmunity. Majeti, R., Xu, Z., Parslow, T.G., Olson, J.L., Daikh, D.I., Killeen, N., Weiss, A. Cell (2000) [Pubmed]
  21. RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Sommer, B., Köhler, M., Sprengel, R., Seeburg, P.H. Cell (1991) [Pubmed]
  22. Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Graf, E.R., Zhang, X., Jin, S.X., Linhoff, M.W., Craig, A.M. Cell (2004) [Pubmed]
  23. Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Li, H., Li, S.H., Johnston, H., Shelbourne, P.F., Li, X.J. Nat. Genet. (2000) [Pubmed]
  24. LIN-10 is a shared component of the polarized protein localization pathways in neurons and epithelia. Rongo, C., Whitfield, C.W., Rodal, A., Kim, S.K., Kaplan, J.M. Cell (1998) [Pubmed]
  25. Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells. Nomura, A., Shigemoto, R., Nakamura, Y., Okamoto, N., Mizuno, N., Nakanishi, S. Cell (1994) [Pubmed]
  26. The opioid peptide dynorphin mediates heterosynaptic depression of hippocampal mossy fibre synapses and modulates long-term potentiation. Weisskopf, M.G., Zalutsky, R.A., Nicoll, R.A. Nature (1993) [Pubmed]
  27. EphB receptors interact with NMDA receptors and regulate excitatory synapse formation. Dalva, M.B., Takasu, M.A., Lin, M.Z., Shamah, S.M., Hu, L., Gale, N.W., Greenberg, M.E. Cell (2000) [Pubmed]
  28. In vivo release of glutamate and aspartate following optic nerve stimulation. Canzek, V., Wolfensberger, M., Amsler, U., Cuénod, M. Nature (1981) [Pubmed]
  29. Expression of functional GABA, glycine and glutamate receptors in Xenopus oocytes injected with rat brain mRNA. Houamed, K.M., Bilbe, G., Smart, T.G., Constanti, A., Brown, D.A., Barnard, E.A., Richards, B.M. Nature (1984) [Pubmed]
  30. Molecular structure of the chick cerebellar kainate-binding subunit of a putative glutamate receptor. Gregor, P., Mano, I., Maoz, I., McKeown, M., Teichberg, V.I. Nature (1989) [Pubmed]
  31. Birth and adaptive evolution of a hominoid gene that supports high neurotransmitter flux. Burki, F., Kaessmann, H. Nat. Genet. (2004) [Pubmed]
  32. Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Das, S., Sasaki, Y.F., Rothe, T., Premkumar, L.S., Takasu, M., Crandall, J.E., Dikkes, P., Conner, D.A., Rayudu, P.V., Cheung, W., Chen, H.S., Lipton, S.A., Nakanishi, N. Nature (1998) [Pubmed]
  33. Neurotrophin-evoked rapid excitation through TrkB receptors. Kafitz, K.W., Rose, C.R., Thoenen, H., Konnerth, A. Nature (1999) [Pubmed]
  34. Control of dynamic CFTR selectivity by glutamate and ATP in epithelial cells. Reddy, M.M., Quinton, P.M. Nature (2003) [Pubmed]
  35. First visualization of glutamate and GABA in neurones by immunocytochemistry. Storm-Mathisen, J., Leknes, A.K., Bore, A.T., Vaaland, J.L., Edminson, P., Haug, F.M., Ottersen, O.P. Nature (1983) [Pubmed]
  36. Regulation of glutamate receptors by cations. Baudry, M., Lynch, G. Nature (1979) [Pubmed]
  37. Magnesium gates glutamate-activated channels in mouse central neurones. Nowak, L., Bregestovski, P., Ascher, P., Herbet, A., Prochiantz, A. Nature (1984) [Pubmed]
  38. Structure of the serine chemoreceptor in Escherichia coli. Boyd, A., Kendall, K., Simon, M.I. Nature (1983) [Pubmed]
  39. Regulation of AMPA receptor lateral movements. Borgdorff, A.J., Choquet, D. Nature (2002) [Pubmed]
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