Glutamate (neurotransmitter): Difference between revisions
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'''Glutamate''' is an [[amino acid]], one of the twenty amino acids used to construct [[protein]]s, and as a consequence is found in high concentration in every part of the body. In the nervous system it plays a special additional role as a [[neurotransmitter]]: a chemical that nerve cells use to send signals to other cells. In fact glutamate is by a wide margin the most abundant neurotransmitter in the vertebrate nervous system.<ref name=Meldrum>{{Cite journal | last1 = Meldrum | first1 = B. S. | title = Glutamate as a neurotransmitter in the brain: Review of physiology and pathology | journal = The Journal of nutrition | volume = 130 | issue = 4S Suppl | pages = 1007S–1015S | year = 2000 | pmid = 10736372}}</ref> At [[synapses|chemical synapses]], glutamate is stored in [[Synaptic vesicle|vesicles]]. [[Nerve impulses]] trigger release of glutamate from the presynaptic cell. Glutamate acts on ionotropic and metabotropic (G-protein coupled) receptors.<ref |
'''Glutamate''' is an [[amino acid]], one of the twenty amino acids used to construct [[protein]]s, and as a consequence is found in high concentration in every part of the body. In the nervous system it plays a special additional role as a [[neurotransmitter]]: a chemical that nerve cells use to send signals to other cells. In fact glutamate is by a wide margin the most abundant neurotransmitter in the vertebrate nervous system.<ref name=Meldrum>{{Cite journal | last1 = Meldrum | first1 = B. S. | title = Glutamate as a neurotransmitter in the brain: Review of physiology and pathology | journal = The Journal of nutrition | volume = 130 | issue = 4S Suppl | pages = 1007S–1015S | year = 2000 | pmid = 10736372 url=http://jn.nutrition.org/content/130/4/1007.full.pdf}}</ref> At [[synapses|chemical synapses]], glutamate is stored in [[Synaptic vesicle|vesicles]]. [[Nerve impulses]] trigger release of glutamate from the presynaptic cell. Glutamate acts on ionotropic and metabotropic (G-protein coupled) receptors.<ref name=Meldrum/> In the opposing postsynaptic cell, [[glutamate receptors]], such as the [[NMDA receptor]] or the [[AMPA receptor]], bind glutamate and are activated. |
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Because of its role in [[synaptic plasticity]], glutamate is involved in cognitive functions such as [[learning]] and [[memory]] in the brain.<ref>{{Cite journal | last1 = McEntee | first1 = W. J. | last2 = Crook | first2 = T. H. | doi = 10.1007/BF02253527 | title = Glutamate: Its role in learning, memory, and the aging brain | journal = Psychopharmacology | volume = 111 | issue = 4 | pages = 391–401 | year = 1993 | pmid = 7870979| pmc = }}</ref> The form of plasticity known as [[long-term potentiation]] takes place at glutamatergic synapses in the [[hippocampus]], [[neocortex]], and other parts of the brain. |
Because of its role in [[synaptic plasticity]], glutamate is involved in cognitive functions such as [[learning]] and [[memory]] in the brain.<ref>{{Cite journal | last1 = McEntee | first1 = W. J. | last2 = Crook | first2 = T. H. | doi = 10.1007/BF02253527 | title = Glutamate: Its role in learning, memory, and the aging brain | journal = Psychopharmacology | volume = 111 | issue = 4 | pages = 391–401 | year = 1993 | pmid = 7870979| pmc = }}</ref> The form of plasticity known as [[long-term potentiation]] takes place at glutamatergic synapses in the [[hippocampus]], [[neocortex]], and other parts of the brain. |
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Glutamate is an amino acid, one of the twenty amino acids used to construct proteins, and as a consequence is found in high concentration in every part of the body. In the nervous system it plays a special additional role as a neurotransmitter: a chemical that nerve cells use to send signals to other cells. In fact glutamate is by a wide margin the most abundant neurotransmitter in the vertebrate nervous system.[1] At chemical synapses, glutamate is stored in vesicles. Nerve impulses trigger release of glutamate from the presynaptic cell. Glutamate acts on ionotropic and metabotropic (G-protein coupled) receptors.[1] In the opposing postsynaptic cell, glutamate receptors, such as the NMDA receptor or the AMPA receptor, bind glutamate and are activated.
Because of its role in synaptic plasticity, glutamate is involved in cognitive functions such as learning and memory in the brain.[2] The form of plasticity known as long-term potentiation takes place at glutamatergic synapses in the hippocampus, neocortex, and other parts of the brain.
Glutamate works not only as a point-to-point transmitter, but also through spill-over synaptic crosstalk between synapses in which summation of glutamate released from a neighboring synapse creates extrasynaptic signaling/volume transmission.[3] In addition, glutamate plays important roles in the regulation of growth cones and synaptogenesis during brain development as originally described by Mark Mattson.
Biosynthesis
Glutamate is a major constituent of a wide variety of proteins; consequently it is one of the most abundant amino acids in the human body.[1] Under ordinary conditions enough is obtained from the diet that there is no need for any to be synthesized. Nevertheless glutamate is formally classified as a non-essential amino acid, because it can be synthesized from alpha-Ketoglutaric acid, which is produced as part of the citric acid cycle by a series of reactions whose starting point is citrate. Glutamate cannot cross the blood-brain barrier unassisted, but it is actively transported into the nervous system by a high affinity transport system, which maintains its concentration in brain fluids at a fairly constant level.[4]
Glutamate itself serves as metabolic precursor for the neurotransmitter GABA, via the action of the enzyme glutamate decarboxylase.
Functions
Cellular effects
Systemic functions
Disease, disorders, and pharmacology
Glutamate transporters,[5] EAAT and VGLUT, are found in neuronal and glial membranes. They rapidly remove glutamate from the extracellular space. In brain injury or disease, they often work in reverse, and excess glutamate can accumulate outside cells. This process causes calcium ions to enter cells via NMDA receptor channels, leading to neuronal damage and eventual cell death, and is called excitotoxicity. The mechanisms of cell death include
- Damage to mitochondria from excessively high intracellular Ca2+[6]
- Glu/Ca2+-mediated promotion of transcription factors for pro-apoptotic genes, or downregulation of transcription factors for anti-apoptotic genes
Excitotoxicity due to excessive glutamate release and impaired uptake occurs as part of the ischemic cascade and is associated with stroke,[7] autism[citation needed], some forms of intellectual disability, and diseases such as amyotrophic lateral sclerosis, lathyrism, and Alzheimer's disease.[7][8] In contrast, decreased glutamate release is observed under conditions of classical phenylketonuria[9] leading to developmental disruption of glutamate receptor expression.[10]
Glutamic acid has been implicated in epileptic seizures. Microinjection of glutamic acid into neurons produces spontaneous depolarisations around one second apart, and this firing pattern is similar to what is known as paroxysmal depolarizing shift in epileptic attacks. This change in the resting membrane potential at seizure foci could cause spontaneous opening of voltage-activated calcium channels, leading to glutamic acid release and further depolarization. [citation needed]
Comparative biology and evolution
Evolution of glutamate receptors is entirely the opposite in invertebrates, in particular, arthropods and nematodes, where glutamate stimulates glutamate-gated chloride channels.[citation needed] The beta subunits of the receptor respond with very high affinity to glutamate and glycine.[11] Targeting these receptors has been the therapeutic goal of anthelmintic therapy using avermectins. Avermectins target the alpha subunit of glutamate-gated chloride channels with high affinity.[12] These receptors have also been described in arthropods, such as Drosophila melanogaster[13] and Lepeophtheirus salmonis.[14] Irreversible activation of these receptors with avermectins results in hyperpolarization at synapses and neuromuscular junctions resulting in flaccid paralysis and death of nematodes and arthropods.
History
References
- ^ a b c Meldrum, B. S. (2000). "Glutamate as a neurotransmitter in the brain: Review of physiology and pathology". The Journal of nutrition. 130 (4S Suppl): 1007S–1015S. PMID url=http://jn.nutrition.org/content/130/4/1007.full.pdf 10736372 url=http://jn.nutrition.org/content/130/4/1007.full.pdf.
{{cite journal}}: Check|pmid=value (help); Missing pipe in:|pmid=(help) - ^ McEntee, W. J.; Crook, T. H. (1993). "Glutamate: Its role in learning, memory, and the aging brain". Psychopharmacology. 111 (4): 391–401. doi:10.1007/BF02253527. PMID 7870979.
- ^ Okubo, Y.; Sekiya, H.; Namiki, S.; Sakamoto, H.; Iinuma, S.; Yamasaki, M.; Watanabe, M.; Hirose, K.; Iino, M. (2010). "Imaging extrasynaptic glutamate dynamics in the brain". Proceedings of the National Academy of Sciences. 107 (14): 6526. doi:10.1073/pnas.0913154107.
- ^ Smith QR (2000). "Transport of glutamate and other amino acids at the blood-brain barrier". J. Nutr. 130 (4S Suppl): 1016S–22S. PMID 10736373. Retrieved 3 December 2015.
- ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/j.brainresrev.2004.04.004, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1016/j.brainresrev.2004.04.004instead. - ^ Manev, H.; Favaron, M.; Guidotti, A.; Costa, E. (1989). "Delayed increase of Ca2+ influx elicited by glutamate: Role in neuronal death". Molecular Pharmacology. 36 (1): 106–112. PMID 2568579.
- ^ a b Robert Sapolsky (2005). "Biology and Human Behavior: The Neurological Origins of Individuality, 2nd edition". The Teaching Company.
see pages 19 and 20 of Guide Book
{{cite news}}: Italic or bold markup not allowed in:|publisher=(help) - ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/j.neuint.2004.03.007, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1016/j.neuint.2004.03.007instead. - ^ Glushakov, AV; Dennis, DM; Sumners, C; Seubert, CN; Martynyuk, AE (Apr 1, 2003). "L-phenylalanine selectively depresses currents at glutamatergic excitatory synapses". Journal of neuroscience research. 72 (1): 116–24. doi:10.1002/jnr.10569. PMID 12645085.
- ^ Glushakov, AV; Glushakova, O; Varshney, M; Bajpai, LK; Sumners, C; Laipis, PJ; Embury, JE; Baker, SP; Otero, DH; Dennis, DM; Seubert, CN; Martynyuk, AE (February 2005). "Long-term changes in glutamatergic synaptic transmission in phenylketonuria". Brain : a journal of neurology. 128 (Pt 2): 300–7. doi:10.1093/brain/awh354. PMID 15634735.
- ^ Laughton, D. L.; Wheeler, S. V.; Lunt, G. G.; Wolstenholme, A. J. (2002). "The β-Subunit of Caenorhabditis elegans Avermectin Receptor Responds to Glycine and is Encoded by Chromosome 1". Journal of Neurochemistry. 64 (5): 2354–2357. doi:10.1046/j.1471-4159.1995.64052354.x. PMID 7536811.
- ^ Cully, D. F.; Vassilatis, D. K.; Liu, K. K.; Paress, P. S.; Van Der Ploeg, L. H. T.; Schaeffer, J. M.; Arena, J. P. (1994). "Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans". Nature. 371 (6499): 707–711. doi:10.1038/371707a0. PMID 7935817.
{{cite journal}}: horizontal tab character in|title=at position 69 (help) - ^ Cully, D.F., Paress, P.S., Liu, K.K., Schaeffer, J.M. and Arena, J.P. 1996. "Identification of a Drosophila melanogaster glutamate-gated chloride channel sensitive to the antiparasitic agent avermectin". J. Biol. Chem. '271, 20187-20191'
- ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1111/j.1365-2885.2007.00823.x, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1111/j.1365-2885.2007.00823.xinstead.