Editing Glutamic acid (section)

== Function and uses ==

=== Metabolism ===
Glutamate is a key compound in cellular [[metabolism]]. In humans, dietary [[proteins]] are broken down by digestion into [[amino acids]], which serve as metabolic fuel for other functional roles in the body. A key process in amino acid degradation is [[transamination]], in which the amino group of an amino acid is transferred to an α-[[Keto acid|ketoacid]], typically catalysed by a [[transaminase]]. The reaction can be generalised as such:

: R<sub>1</sub>-amino acid + R<sub>2</sub>-α-[[Keto acid|ketoacid]] ⇌ R<sub>1</sub>-α-ketoacid + R<sub>2</sub>-amino acid

A very common α-keto acid is [[α-ketoglutarate]], an intermediate in the [[citric acid cycle]]. Transamination of α-ketoglutarate gives glutamate. The resulting α-ketoacid product is often a useful one as well, which can contribute as fuel or as a substrate for further metabolism processes. Examples are as follows:

: [[alanine]] + α-ketoglutarate ⇌ [[pyruvate]] + glutamate

: [[aspartate]] + α-ketoglutarate ⇌ [[oxaloacetate]] + glutamate

Both [[pyruvate]] and [[oxaloacetate]] are key components of cellular metabolism, contributing as substrates or intermediates in fundamental processes such as [[glycolysis]], [[gluconeogenesis]], and the [[citric acid cycle]].

Glutamate also plays an important role in the body's disposal of excess or waste [[nitrogen]]. Glutamate undergoes [[deamination]], an oxidative reaction catalysed by [[glutamate dehydrogenase]],<ref name="springerlink" /> as follows:

: glutamate + H<sub>2</sub>O + [[Nicotinamide adenine dinucleotide phosphate|NADP]]<sup>+</sup> → α-ketoglutarate + [[Nicotinamide adenine dinucleotide phosphate|NADPH]] + NH<sub>3</sub> + H<sup>+</sup>

Ammonia (as [[ammonium]]) is then excreted predominantly as [[urea]], synthesised in the [[liver]]. Transamination can thus be linked to deamination, effectively allowing nitrogen from the amine groups of amino acids to be removed, via glutamate as an intermediate, and finally excreted from the body in the form of urea.

Glutamate is also a [[neurotransmitter]] (see below), which makes it one of the most abundant molecules in the brain. Malignant brain tumors known as [[glioma]] or [[glioblastoma]] exploit this phenomenon by using glutamate as an energy source, especially when these tumors become more dependent on glutamate due to mutations in the gene [[IDH1]].<ref>{{cite journal|last1=van Lith|first1=SA|last2=Navis|first2=AC|last3=Verrijp|first3=K|last4=Niclou|first4=SP|last5=Bjerkvig|first5=R|last6=Wesseling|first6=P|last7=Tops|first7=B|last8=Molenaar|first8=R|last9=van Noorden|first9=CJ|last10=Leenders|first10=WP|title=Glutamate as chemotactic fuel for diffuse glioma cells: are they glutamate suckers?|journal=Biochimica et Biophysica Acta (BBA) - Reviews on Cancer|date=August 2014|volume=1846|issue=1|pages=66–74|pmid=24747768|doi=10.1016/j.bbcan.2014.04.004|url=https://orbilu.uni.lu/handle/10993/60245 }}</ref><ref>{{cite journal|last1=van Lith|first1=SA|last2=Molenaar|first2=R|last3=van Noorden|first3=CJ|last4=Leenders|first4=WP|title=Tumor cells in search for glutamate: an alternative explanation for increased invasiveness of IDH1 mutant gliomas|journal=Neuro-Oncology|date=December 2014|volume=16|issue=12|pages=1669–1670|pmid=25074540|doi=10.1093/neuonc/nou152|pmc=4232089}}</ref>

{{see also|Glutamate–glutamine cycle}}

=== Neurotransmitter ===
{{main|Glutamate (neurotransmitter)}}

Glutamate is the most abundant excitatory [[neurotransmitter]] in the vertebrate [[nervous system]].<ref name="pmid10736372">{{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
 | doi=10.1093/jn/130.4.1007s
| doi-access = free
}}</ref> At [[synapses|chemical synapses]], glutamate is stored in [[Synaptic vesicle|vesicles]]. [[Nerve impulses]] trigger the release of glutamate from the [[presynaptic]] cell. Glutamate acts on [[ionotropic]] and [[Metabotropic receptor|metabotropic]] ([[G protein-coupled receptor|G-protein coupled]]) receptors.<ref name="pmid10736372"/>  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 function]]s 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| s2cid = 37400348 }}</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. Glutamate works not only as a [[Point-to-point (telecommunications)|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]].<ref>{{Cite journal | last1 = Okubo | first1 = Y. | last2 = Sekiya | first2 = H. | last3 = Namiki | first3 = S. | last4 = Sakamoto | first4 = H. | last5 = Iinuma | first5 = S. | last6 = Yamasaki | first6 = M. | last7 = Watanabe | first7 = M. | last8 = Hirose | first8 = K. | last9 = Iino | first9 = M. | doi = 10.1073/pnas.0913154107 | title = Imaging extrasynaptic glutamate dynamics in the brain | journal = Proceedings of the National Academy of Sciences | volume = 107 | issue = 14 | pages = 6526–6531 | year = 2010 | pmid =  20308566| pmc = 2851965| bibcode = 2010PNAS..107.6526O | doi-access = free }}</ref>  In addition, glutamate plays important roles in the regulation of [[growth cone]]s and [[synaptogenesis]] during [[brain development]] as originally described by [[Mark Mattson]].

=== Brain nonsynaptic glutamatergic signaling circuits ===
Extracellular glutamate in ''[[Drosophila]]'' brains has been found to regulate postsynaptic glutamate receptor clustering, via a process involving receptor desensitization.<ref name = augustin>{{cite journal |vauthors=Augustin H, Grosjean Y, Chen K, Sheng Q, Featherstone DE | title=Nonvesicular Release of Glutamate by Glial xCT Transporters Suppresses Glutamate Receptor Clustering In Vivo | journal=Journal of Neuroscience | volume=27 | issue=1 | year=2007 | pages=111–123 | pmid=17202478 | doi = 10.1523/JNEUROSCI.4770-06.2007 | pmc=2193629}}</ref> A gene expressed in [[glial cell]]s actively transports glutamate into the [[extracellular space]],<ref name = augustin/> while, in the [[nucleus accumbens]]-stimulating group II [[metabotropic glutamate receptor]]s, this gene was found to reduce extracellular glutamate levels.<ref>{{cite journal |author1=Zheng Xi |author2=Baker DA |author3=Shen H |author4=Carson DS |author5=Kalivas PW | title=Group II metabotropic glutamate receptors modulate extracellular glutamate in the nucleus accumbens | journal=Journal of Pharmacology and Experimental Therapeutics | volume=300 | issue=1 | year=2002 | pages=162–171 | pmid=11752112 | doi=10.1124/jpet.300.1.162}}</ref> This raises the possibility that this extracellular glutamate plays an "endocrine-like" role as part of a larger homeostatic system.

==== GABA precursor ====
Glutamate also serves as the precursor for the synthesis of the inhibitory [[gamma-aminobutyric acid]] (GABA) in GABA-ergic neurons. This reaction is catalyzed by [[glutamate decarboxylase]] (GAD).<ref>{{Cite journal |last1=Bak |first1=Lasse K. |last2=Schousboe |first2=Arne |last3=Waagepetersen |first3=Helle S. |date=August 2006 |title=The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer |url=https://pubmed.ncbi.nlm.nih.gov/16787421/ |journal=Journal of Neurochemistry |volume=98 |issue=3 |pages=641–653 |doi=10.1111/j.1471-4159.2006.03913.x |issn=0022-3042 |pmid=16787421}}</ref> GABA-ergic neurons are identified (for research purposes) by revealing its activity (with the [[autoradiograph]]y and [[immunohistochemistry]] methods)<ref>{{Cite journal |last1=Kerr |first1=D.I.B. |last2=Ong |first2=J. |date=January 1995 |title=GABA<sub>B</sub> receptors |url=https://linkinghub.elsevier.com/retrieve/pii/016372589500016A |journal=Pharmacology & Therapeutics |language=en |volume=67 |issue=2 |pages=187–246 |doi=10.1016/0163-7258(95)00016-A |pmid=7494864 |url-access=subscription}}</ref> which is most abundant in the [[cerebellum]] and [[pancreas]].<ref>{{Cite book |last1=Krueger |first1=Christian |title=Autoantibodies |last2=Stöker |first2=Winfried |last3=Schlosser |first3=Michael |year=2007 |edition=2nd |publication-date=2007 |pages=369–378 |language=en |chapter=GLUTAMIC ACID DECARBOXYLASE AUTOANTIBODIES |doi=10.1016/B978-044452763-9/50052-4 |isbn=978-0-444-52763-9 |chapter-url=https://www.sciencedirect.com/science/article/pii/B9780444527639500524 |chapter-url-access=subscription}}</ref>

[[Stiff person syndrome]] is a neurologic disorder caused by anti-GAD antibodies, leading to a decrease in GABA synthesis and, therefore, impaired motor function such as muscle stiffness and spasm. Since the pancreas has abundant GAD, a direct immunological destruction occurs in the pancreas and the patients will have [[diabetes mellitus]].<ref>{{Cite journal |last1=Newsome |first1=Scott D. |last2=Johnson |first2=Tory |date=2022-08-15 |title=Stiff Person Syndrome Spectrum Disorders; More Than Meets the Eye |journal=Journal of Neuroimmunology |volume=369 |pages=577915 |doi=10.1016/j.jneuroim.2022.577915 |issn=0165-5728 |pmc=9274902 |pmid=35717735}}</ref>

=== Flavor enhancer ===
{{Main|Glutamate flavoring}}
Glutamic acid, being a constituent of protein, is present in foods that contain protein, but it can only be tasted when it is present in an unbound form.  Significant amounts of free glutamic acid are present in a wide variety of foods, including [[cheese]]s and [[soy sauce]], and glutamic acid is responsible for [[umami]], one of the five [[basic taste]]s of the human sense of [[taste]]. Glutamic acid often is used as a [[food additive]] and [[flavor enhancer]] in the form of its sodium [[salt (chemistry)|salt]], known as monosodium glutamate (MSG).

=== Nutrient ===
All meats, poultry, fish, eggs, dairy products, and [[kombu]] are excellent sources of glutamic acid. Some protein-rich plant foods also serve as sources.  30% to 35% of gluten (much of the protein in wheat) is glutamic acid. Ninety-five percent of the dietary glutamate is metabolized by intestinal cells in a first pass.<ref>{{cite journal | author=Reeds, P.J.| title=Intestinal glutamate metabolism | journal=Journal of Nutrition | volume=130 | issue=4s | date=1 April 2000| pages=978S–982S | pmid=10736365 |display-authors=etal| doi=10.1093/jn/130.4.978S | doi-access=free }}</ref>

=== Plant growth ===
[[Auxigro]] is a plant growth preparation that contains 30% glutamic acid.

=== NMR spectroscopy ===
In recent years,{{when|date=October 2018}} there has been much research into the use of [[residual dipolar coupling]] (RDC) in [[nuclear magnetic resonance spectroscopy]] (NMR). A glutamic acid derivative, [[poly-γ-benzyl-L-glutamate]] (PBLG), is often used as an alignment medium to control the scale of the dipolar interactions observed.<ref>C. M. Thiele, Concepts Magn. Reson. A, 2007, 30A, 65–80</ref>

=== Glutamate and aging ===
{{See also|Aging brain#Glutamate}}
Brain glutamate levels tend to decline with age, and may be a useful as a marker of age-related diseases of the brain.<ref>{{cite journal |last1=Chang |first1=Linda |last2=Jiang |first2=Caroline S. |last3=Ernst |first3=Thomas |title=Effects of age and sex on brain glutamate and other metabolites |journal=Magnetic Resonance Imaging |date=1 January 2009 |volume=27 |issue=1 |pages=142–145 |doi=10.1016/j.mri.2008.06.002 |pmid=18687554 |issn=0730-725X|pmc=3164853 }}</ref>