Editing Glutamic acid

{{short description|Amino acid and neurotransmitter}}
{{distinguish|Glutamine|Glutaric acid|Gluten}}
{{For|the anion in its role as a neurotransmitter|Glutamate (neurotransmitter)}}
{{Use dmy dates|date=April 2023}}
{{Chembox
| ImageFile1     = L-Glutaminsäure - L-Glutamic acid.svg
| ImageClass1    = skin-invert-image
| ImageName1     = Glutamic acid in non ionic form
| ImageCaption1  = [[Skeletal formula]] of {{sc|L}}-glutamic acid
| ImageFileL2    = Glutamic-acid-from-xtal-view-2-3D-bs-17.png
| ImageClassL2   = bg-transparent
| ImageSizeL2    = 100
| ImageCaptionL2 = [[Ball-and-stick model]]
| ImageFileR2    = Glutamic-acid-from-xtal-view-2-3D-sf.png
| ImageClassR2   = bg-transparent
| ImageSizeR2    = 110
| ImageCaptionR2 = [[Space-filling model]]
| ImageFile3     = Sample of L-Glutamic acid.jpg
| ImageSize3     = 100px
| SystematicName = 2-Aminopentanedioic acid
| OtherNames     = {{Unbulleted list|2-Aminoglutaric acid}}
| IUPACName      = Glutamic acid
| Section1       = {{Chembox Identifiers
| index_label = {{sm|l}} isomer
| index1_label= racemate
| index2_label={{sm|d}} isomer
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII1_Ref = {{fdacite|correct|FDA}}
| UNII2_Ref = {{fdacite|correct|FDA}}
| UNII = 3KX376GY7L
| UNII1 = 61LJO5I15S
| UNII2 = Q479989WEA
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C00025
| KEGG2 = C00217
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 30572
| InChI = 1/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)
| InChIKey = WHUUTDBJXJRKMK-UHFFFAOYAD
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = WHUUTDBJXJRKMK-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo =  56-86-0
| CASNo1_Ref = {{cascite|correct|CAS}}
| CASNo1 = 617-65-2
| CASNo2_Ref = {{cascite|correct|CAS}}
| CASNo2 = 6893-26-1
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 16015
| ChEBI1 = 18237
| ChEBI2 = 15966
| ChEMBL = 575060
| PubChem = 33032
| PubChem2 = 23327
| EC_number = 200-293-7
| DrugBank = DB00142
| DrugBank2 = DB02517
| 3DMet = B00007
| Beilstein = 1723801 (L) 1723799 (rac) 1723800 (D)
| Gmelin = 3502 (L) 101971 (rac) 201189 (D)
| SMILES = C(CC(=O)O)[C@@H](C(=O)O)N
| SMILES2 = C(CC(=O)O)[C@H](C(=O)O)N
| SMILES3 = C(CC(=O)O)C(C(=O)[O-])[NH3+]
| SMILES3_Comment = [[Zwitterion]]
| SMILES4 = C(CC(=O)[O-])C(C(=O)[O-])[NH3+]
| SMILES4_Comment = Deprotonated zwitterion
}}
| Section2       = {{Chembox Properties
| C=5 | H=9 | N=1 | O=4
| Appearance = White crystalline powder
| Density = 1.4601 (20&nbsp;°C)
| MeltingPtC = 199
| MeltingPt_notes = decomposes
| Solubility = 8.57&nbsp;g/L (25 °C)<ref name="NLM">{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/33032|title=L-Glutamic acid| publisher=National Library of Medicine|access-date=24 June 2023}}</ref>
| SolubleOther = Ethanol: 350&nbsp;μg/100{{nnbsp}}g (25&nbsp;°C)<ref>{{Cite book| url = https://books.google.com/books?id=xteiARU46SQC&pg=PA15 | title = Food Chemistry | isbn = 978-3540699330 | last1 = Belitz | first1 = H.-D. | last2 = Grosch | first2 = Werner | last3 = Schieberle | first3 = Peter | date = 2009-02-27| publisher = Springer }}</ref>
| pKa = 2.10, 4.07, 9.47<ref>{{cite web | url=http://www.cem.msu.edu/~cem252/sp97/ch24/ch24aa.html | title=Amino Acid Structures | publisher=cem.msu.edu | archive-url=https://web.archive.org/web/19980211015420/http://www.cem.msu.edu/~cem252/sp97/ch24/ch24aa.html | archive-date=1998-02-11}}</ref>
| MagSus = −78.5·10<sup>−6</sup> cm<sup>3</sup>/mol
  }}
| Section3       = 
| Section4       = 
| Section5       = 
| Section6       = 
| Section7       = {{Chembox Hazards
| NFPA-H = 2
| NFPA-F = 1
| NFPA-R = 0
| FlashPt =
| GHSPictograms = {{GHS07}}
| GHSSignalWord = Warning
| HPhrases = {{H-phrases|315|319|335}}
| PPhrases = {{P-phrases|261|264|271|280|302+352|304+340|305+351+338|312|321|332+313|337+313|362|403+233|405|501}}
 }}
}}
[[File:Glutamic acid-spin.gif|thumb|Glutamic acid ball and stick model spinning]]
'''Glutamic acid''' (symbol '''Glu''' or '''E''';<ref>{{cite web | url = http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html | title = Nomenclature and Symbolism for Amino Acids and Peptides | publisher = IUPAC-IUB Joint Commission on Biochemical Nomenclature | year = 1983 | access-date = 2018-03-05 | archive-url = https://web.archive.org/web/20170829151742/http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html | archive-date = 2017-08-29 | url-status = dead }}</ref> known as '''glutamate''' in its anionic form) is an α-[[amino acid]] that is used by almost all living beings in the [[biosynthesis]] of [[protein]]s. It is a [[Essential amino acid|non-essential nutrient]] for humans, meaning that the human body can synthesize enough for its use. It is also the most abundant excitatory [[neurotransmitter]] in the vertebrate [[nervous system]]. It serves as the precursor for the synthesis of the inhibitory [[gamma-aminobutyric acid]] (GABA) in GABAergic neurons.

Its molecular formula is {{chem|C|5|H|9|N|O|4}}. Glutamic acid exists in two optically isomeric forms; the [[optical rotation|dextrorotatory]] {{sc|L}}-form is usually obtained by hydrolysis of [[gluten]] or from the waste waters of [[beet]]-sugar manufacture or by fermentation.<ref name = Web1>Webster's Third New International Dictionary of the English Language Unabridged, Third Edition, 1971.</ref>{{full|date=April 2023}} Its molecular structure could be idealized as HOOC−CH({{chem|N|H|2|}})−({{chem|C|H|2}})<sub>2</sub>−COOH, with two [[carboxylic acid|carboxyl]] groups −COOH and one [[amine|amino group]] −{{chem|N|H|2|}}. However, in the solid state and mildly [[acid]]ic water solutions, the molecule assumes an [[electric charge|electrically neutral]] [[zwitterion]] structure <sup>−</sup>OOC−CH({{chem|N|H|3|+}})−({{chem|C|H|2}})<sub>2</sub>−COOH. It is [[Genetic code|encoded]] by the [[codon]]s GAA or GAG.

The acid can lose one [[proton]] from its second [[carboxyl group]] to form the [[conjugate base]], the singly-negative [[anion]] '''glutamate''' <sup>−</sup>OOC−CH({{chem|N|H|3|+}})−({{chem|C|H|2}})<sub>2</sub>−COO<sup>−</sup>. This form of the compound is prevalent in [[acidity|neutral]] solutions. The [[glutamate (neurotransmitter)|glutamate neurotransmitter]] plays the principal role in [[neuron|neural activation]].<ref name="twsNovK11">[[Robert Sapolsky]] (2005), ''Biology and Human Behavior: The Neurological Origins of Individuality'' (2nd edition); [[The Teaching Company]]. pp. 19–20 of the Guide Book.</ref> This anion creates the savory ''[[umami]]'' flavor of foods and is found in [[glutamate flavoring]]s such as [[monosodium glutamate]] (MSG). In Europe, it is classified as food additive [[E-numbers|E620]]. In highly [[alkali]]ne solutions the doubly negative anion <sup>−</sup>OOC−CH({{chem|N|H|2}})−({{chem|C|H|2}})<sub>2</sub>−COO<sup>−</sup> prevails. The [[radical (chemistry)|radical]] corresponding to glutamate is called '''glutamyl'''.

The one-letter symbol E for glutamate was assigned as the letter following D for [[aspartic acid|aspartate]], as glutamate is larger by one [[methylene group|methylene]] –CH<sub>2</sub>– group.<ref name=":1">{{Cite journal |last=Saffran |first=M. |date=April 1998 |title=Amino acid names and parlor games: from trivial names to a one-letter code, amino acid names have strained students' memories. Is a more rational nomenclature possible? |url=http://linkinghub.elsevier.com/retrieve/pii/S0307441297001672 |journal=Biochemical Education |language=en |volume=26 |issue=2 |pages=116–118 |doi=10.1016/S0307-4412(97)00167-2}}</ref>

== Chemistry ==
===Ionization===
[[File:Glutamic Acid at physiological pH V2.svg|class=skin-invert-image|thumb|left|The glutamate monoanion.]]
When glutamic acid is dissolved in water, the [[amine|amino group]] (−{{chem|N|H|2}}) may gain a [[proton]] ({{chem|H|+}}), and/or the [[carboxylic acid|carboxyl groups]] may lose protons, depending on the [[pH|acidity]] of the medium.

In sufficiently acidic environments, both carboxyl groups are protonated and the molecule becomes a [[cation]] with a single positive charge, HOOC−CH({{chem|N|H|3|+}})−({{chem|C|H|2}})<sub>2</sub>−COOH.<ref name=neub>{{cite journal|pmc=1263308 |date=1936 |last1=Neuberger |first1=A. |title=Dissociation constants and structures of glutamic acid and its esters |journal=Biochemical Journal |volume=30 |issue=11 |pages=2085–2094 |doi=10.1042/bj0302085 |pmid=16746266 }}</ref>

At [[pH]] values between about 2.5 and 4.1,<ref name=neub/> the carboxylic acid closer to the amine generally loses a proton, and the acid becomes the neutral zwitterion <sup>−</sup>OOC−CH({{chem|N|H|3|+}})−({{chem|C|H|2}})<sub>2</sub>−COOH. This is also the form of the compound in the crystalline solid state.<ref name=roda>{{cite journal | last1 = Rodante | first1 = F. | last2 = Marrosu | first2 = G. | year = 1989 | title = Thermodynamics of the second proton dissociation processes of nine α-amino-acids and the third ionization processes of glutamic acid, aspartic acid and tyrosine | journal = Thermochimica Acta | volume = 141 | pages = 297–303 | doi = 10.1016/0040-6031(89)87065-0 | bibcode = 1989TcAc..141..297R }}</ref><ref name=cryst>{{cite journal | last1 = Lehmann | first1 = Mogens S. | last2 = Koetzle | first2 = Thomas F. | last3 = Hamilton | first3 = Walter C. | year = 1972 | title = Precision neutron diffraction structure determination of protein and nucleic acid components. VIII: the crystal and molecular structure of the β-form of the amino acidl-glutamic acid | journal = Journal of Crystal and Molecular Structure | volume = 2 | issue = 5| pages = 225–233 | doi = 10.1007/BF01246639 | bibcode = 1972JCCry...2..225L | s2cid = 93590487 }}</ref>  The change in protonation state is gradual; the two forms are in equal concentrations at pH 2.10.<ref name=ionpH/>

At even higher pH, the other carboxylic acid group loses its proton and the acid exists almost entirely as the glutamate anion <sup>−</sup>OOC−CH({{chem|N|H|3|+}})−({{chem|C|H|2}})<sub>2</sub>−COO<sup>−</sup>, with a single negative charge overall. The change in protonation state occurs at pH 4.07.<ref name=ionpH/> This form with both carboxylates lacking protons is dominant in the [[physiological pH]] range (7.35–7.45).

At even higher pH, the amino group loses the extra proton, and the prevalent species is the doubly-negative anion <sup>−</sup>OOC−CH({{chem|N|H|2}})−({{chem|C|H|2}})<sub>2</sub>−COO<sup>−</sup>. The change in protonation state occurs at pH 9.47.<ref name=ionpH>William H. Brown and Lawrence S. Brown (2008), ''Organic Chemistry'' (5th edition). Cengage Learning. p. 1041. {{ISBN|0495388572|978-0495388579}}.</ref>

===Optical isomerism===
Glutamic acid is [[chiral]]; two mirror-image [[Enantiomer|enantiomers]] exist: {{sm|d}}(−), and {{sm|l}}(+). The {{sm|l}} form is more widely occurring in nature, but the {{sm|d}} form occurs in some special contexts, such as the [[bacterial capsule]] and [[cell wall]]s of the [[bacteria]] (which produce it from the {{sm|l}} form with the [[enzyme]] [[glutamate racemase]]) and the [[liver]] of [[mammals]].<ref name=Dglut>National Center for Biotechnology Information, "[https://pubchem.ncbi.nlm.nih.gov/compound/23327 D-glutamate]". ''PubChem Compound Database'', CID=23327. Accessed 2017-02-17.</ref><ref name=DgEcoli>{{cite journal | last1 = Liu | first1 = L. | last2 = Yoshimura | first2 = T. | last3 = Endo | first3 = K. | last4 = Kishimoto | first4 = K. | last5 = Fuchikami | first5 = Y. | last6 = Manning | first6 = J. M. | last7 = Esaki | first7 = N. | last8 = Soda | first8 = K. | year = 1998 | title = Compensation for {{sc|D}}-glutamate auxotrophy of ''Escherichia coli'' WM335 by {{sc|D}}-amino acid aminotransferase gene and regulation of ''murI'' expression | journal = Bioscience, Biotechnology, and Biochemistry | volume = 62 | issue = 1 | pages = 193–195 | doi = 10.1271/bbb.62.193 | pmid = 9501533 | doi-access = free }}</ref>
<!-- ref name=Dglut
{{sm|d}}-glutamate is also present in certain foods e.g., soybeans and also arises from the turnover of the intestinal tract microflora, whose cell walls contain significant {{sm|d}}-glutamate. Unlike other {{sm|d}}-amino acids, {{sm|d}}-glutamate is not oxidized by the {{sm|d}}-amino acid oxidases, and therefore this detoxification pathway is not available for handling {{sm|d}}-glutamate. Likewise, {{sm|d}}-glutamic acid, when ingested, largely escapes most deamination reactions (unlike the {{sm|l}}-counterpart). Free {{sm|d}}-glutamate is found in mammalian tissue at surprisingly high levels, with {{sm|d}}-glutamate accounting for 9% of the total glutamate present in liver. {{sm|d}}-glutamate is the most potent natural inhibitor of glutathione synthesis identified to date and this may account for its localization to the liver, since circulating {{sm|d}}-glutamate may alter redox stability ({{cite journal | pmid = 11158923 | volume=280 | title=Regulatory responses to an oral D-glutamate load: formation of D-pyrrolidone carboxylic acid in humans | year=2001 | journal=Am J Physiol Endocrinol Metab | pages=E214-20  | last1 = Raj | first1 = D | last2 = Langford | first2 = M | last3 = Krueger | first3 = S | last4 = Shelton | first4 = M | last5 = Welbourne | first5 = T | doi = 10.1152/ajpendo.2001.280.2.e214}}). Certain eels are known to use {{sm|d}}-glutamic acid as a pheromone for chemical communication.-->

==History==
{{Main|Glutamic acid (flavor)}}
Although they occur naturally in many foods, the flavor contributions made by glutamic acid and other amino acids were only scientifically identified early in the 20th century. The substance was discovered and identified in the year 1866 by the German chemist [[Karl Heinrich Ritthausen]], who treated wheat [[gluten]] (for which it was named) with [[sulfuric acid]].<ref>{{cite book |author= [[R. H. A. Plimmer]] |editor1=R. H. A. Plimmer |editor2=F. G. Hopkins |title= The Chemical Constitution of the Protein |url= https://books.google.com/books?id=7JM8AAAAIAAJ&pg=PA114 |access-date= June 3, 2012 |edition= 2nd |series= Monographs on biochemistry |volume= Part I. Analysis |orig-year= 1908 |year= 1912 |publisher= Longmans, Green and Co. |location= London |page= 114}}</ref> In 1908, Japanese researcher [[Kikunae Ikeda]] of the [[Tokyo Imperial University]] identified brown crystals left behind after the evaporation of a large amount of [[kombu]] broth as glutamic acid. These crystals, when tasted, reproduced the novel flavor he detected in many foods, most especially in seaweed. Professor Ikeda termed this flavor [[umami]]. He then patented a method of mass-producing a crystalline salt of glutamic acid, monosodium glutamate.<ref name="guardian">{{cite news |url=http://observer.guardian.co.uk/foodmonthly/story/0,,1522368,00.html |title = If MSG is so bad for you, why doesn't everyone in Asia have a headache? |newspaper = [[The Guardian]] |last = Renton |first = Alex |date = 2005-07-10 |access-date= 2008-11-21}}</ref><ref>{{cite web |url = http://www.jpo.go.jp/seido_e/rekishi_e/kikunae_ikeda.htm |title = Kikunae Ikeda Sodium Glutamate |date = 2002-10-07 |access-date = 2008-11-21 |publisher = [[Japan Patent Office]] |archive-url = https://web.archive.org/web/20071028131520/http://www.jpo.go.jp/seido_e/rekishi_e/kikunae_ikeda.htm |archive-date = 2007-10-28 |url-status = dead}}</ref>

==Synthesis==
===Biosynthesis===
{| align="left" cellspacing="0" cellpadding="3" style="background: #FFFFFF; border: 1px solid #C0C090;"
! style="background-color: #F8EABA;" | [[Reactants]]
! style="background-color: #F8EABA;" |
! style="background-color: #F8EABA;" | [[Product (chemistry)|Products]]
! style="background-color: #F8EABA;" | [[Enzymes]]
|-
| [[glutamine]] + [[water|H<sub>2</sub>O]] || → || '''Glu''' + [[ammonia|NH<sub>3</sub>]]
| [[Protein:GLS|GLS]], [[Protein:GLS2|GLS2]]
|-
| [[N acetylglutamic acid|NAcGlu]] + [[water|H<sub>2</sub>O]] || → || '''Glu''' + [[acetate]]
| ''N''-acetyl-glutamate synthase
|-
| [[Alpha-Ketoglutaric acid|α-ketoglutarate]] + [[NADP]]H + NH<sub>4</sub><sup>+</sup> || → || '''Glu''' + [[NADP]]<sup>+</sup> + H<sub>2</sub>O
| [[Protein:GLUD1|GLUD1]], [[Protein:GLUD2|GLUD2]]<ref name="springerlink">{{Cite journal | last1 = Grabowska | first1 = A. | last2 = Nowicki | first2 = M. | last3 = Kwinta | first3 = J. | doi = 10.1007/s11738-011-0801-1 | title = Glutamate dehydrogenase of the germinating triticale seeds: Gene expression, activity distribution and kinetic characteristics | journal = Acta Physiologiae Plantarum | volume = 33 | issue = 5 | pages = 1981–1990 | year = 2011 | doi-access = free | bibcode = 2011AcPPl..33.1981G }}</ref>
|-
| [[Alpha-Ketoglutaric acid|α-ketoglutarate]] + [[amino acid|α-amino acid]] || → || '''Glu''' + [[keto acid|α-keto acid]]
| [[transaminase]]
|-
| [[1-pyrroline-5-carboxylate]] + [[nicotinamide adenine dinucleotide|NAD<sup>+</sup>]] + H<sub>2</sub>O || → || '''Glu''' + NADH
| [[Protein:ALDH4A1|ALDH4A1]]
|-
| [[N-formimino-L-glutamate]] + [[folic acid|FH<sub>4</sub>]] || → || '''Glu''' + [[folic acid|5-formimino-FH<sub>4</sub>]]
| [[Protein:FTCD|FTCD]]
|-
| [[N-Acetylaspartylglutamic acid|NAAG]] || → || '''Glu''' + NAA
| [[Glutamate carboxypeptidase II|GCPII]]
|}
{{clear|left}}

===Industrial synthesis===
Glutamic acid is produced on the largest scale of any amino acid, with an estimated annual production of about 1.5 million tons in 2006.<ref name="PerosaZecchini2007">{{cite book|author1=Alvise Perosa|author2=Fulvio Zecchini|title=Methods and Reagents for Green Chemistry: An Introduction|url=https://books.google.com/books?id=jtS9DH54vjUC&pg=PA189|date=2007|publisher=John Wiley & Sons|isbn=978-0-470-12407-9|page=25}}</ref> Chemical synthesis was supplanted by the [[aerobic fermentation]] of sugars and ammonia in the 1950s, with the organism ''[[Corynebacterium glutamicum]]'' (also known as ''Brevibacterium flavum'') being the most widely used for production.<ref name="Flickinger2010">{{cite book|author=Michael C. Flickinger|title=Encyclopedia of Industrial Biotechnology: Bioprocess, Bioseparation, and Cell Technology, 7 Volume Set|url=https://books.google.com/books?id=W_2hMwEACAAJ|date=2010|publisher=Wiley|isbn=978-0-471-79930-6|pages=215–225}}</ref> Isolation and purification can be achieved by concentration and [[crystallization]]; it is also widely available as its [[hydrochloride]] salt.<ref name="FoleyKermanshahi pour2012">{{cite journal|last1=Foley|first1=Patrick|last2=Kermanshahi pour|first2=Azadeh|last3=Beach|first3=Evan S.|last4=Zimmerman|first4=Julie B.|title=Derivation and synthesis of renewable surfactants|journal=Chem. Soc. Rev.|volume=41|issue=4|year=2012|pages=1499–1518|issn=0306-0012|doi=10.1039/C1CS15217C|pmid=22006024}}</ref>

== 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>

== Pharmacology ==
The drug [[phencyclidine]] (more commonly known as PCP or 'Angel Dust') [[Receptor antagonist|antagonizes]] glutamic acid [[Non-competitive antagonism|non-competitively]] at the [[NMDA receptor]]. For the same reasons, [[dextromethorphan]] and [[ketamine]] also have strong [[dissociative]] and [[hallucinogen]]ic effects. Acute infusion of the drug [[eglumetad]] (also known as eglumegad or LY354740), an [[agonist]] of the [[metabotropic glutamate receptor]]s [[metabotropic glutamate receptor 2|2]] and [[metabotropic glutamate receptor 3|3]]) resulted in a marked diminution of [[yohimbine]]-induced [[stress response]] in bonnet macaques (''[[Macaca radiata]]''); chronic oral administration of eglumetad in those animals led to markedly reduced baseline [[cortisol]] levels (approximately 50 percent) in comparison to untreated control subjects.<ref>{{cite journal |vauthors=Coplan JD, Mathew SJ, Smith EL, Trost RC, Scharf BA, Martinez J, Gorman JM, Monn JA, Schoepp DD, Rosenblum LA |title=Effects of LY354740, a novel glutamatergic metabotropic agonist, on nonhuman primate hypothalamic-pituitary-adrenal axis and noradrenergic function |journal=CNS Spectr. |volume=6 |issue=7 |pages=607–612, 617|date=July 2001 |pmid=15573025 |doi= 10.1017/S1092852900002157|s2cid=6029856 }}</ref> Eglumetad has also been demonstrated to act on the [[metabotropic glutamate receptor 3]] (GRM3) of human [[adrenal cortex|adrenocortical cells]], downregulating [[aldosterone synthase]], [[CYP11B1]], and the production of [[adrenal]] [[steroid]]s (i.e. [[aldosterone]] and [[cortisol]]).<ref>{{cite journal |vauthors=Felizola SJ, Nakamura Y, Satoh F, Morimoto R, Kikuchi K, Nakamura T, Hozawa A, Wang L, Onodera Y, Ise K, McNamara KM, Midorikawa S, Suzuki S, Sasano H |title=Glutamate receptors and the regulation of steroidogenesis in the human adrenal gland: The metabotropic pathway |journal=Molecular and Cellular Endocrinology |volume=382 |issue=1 |pages=170–177|date=January 2014|pmid=24080311 |doi=10.1016/j.mce.2013.09.025 |s2cid=3357749 }}</ref> Glutamate does not easily pass the [[blood brain barrier]], but, instead, is transported by a high-affinity transport system.<ref>{{cite journal |last1=Smith |first1=Quentin R. |title=Transport of glutamate and other amino acids at the blood–brain barrier |journal=[[The Journal of Nutrition]] |volume=130 |issue=4S Suppl |pages=1016S–1022S |date=April 2000 |pmid=10736373 |doi= 10.1093/jn/130.4.1016S|doi-access=free }}</ref><ref>{{cite journal |last=Hawkins |first=Richard A. |date=September 2009 |title=The blood-brain barrier and glutamate |journal=[[The American Journal of Clinical Nutrition]] |volume=90 |issue=3 |pages=867S–874S |doi=10.3945/ajcn.2009.27462BB |pmid=19571220 |quote=This organization does not allow net glutamate entry to the brain; rather, it promotes the removal of glutamate and the maintenance of low glutamate concentrations in the ECF. |pmc=3136011 }}</ref> It can also be converted into [[glutamine]].

Glutamate toxicity can be reduced by [[Antioxidant|antioxidants]], and the psychoactive principle of [[Cannabis (drug)|cannabis]], [[tetrahydrocannabinol]] (THC), and the non psychoactive principle [[cannabidiol]] (CBD), and other [[Cannabinoid|cannabinoids]], is found to block glutamate [[neurotoxicity]] with a similar potency, and thereby potent antioxidants.<ref>{{Cite journal |last=Hampson |first=Aidan J. |date=1998 |title=Cannabidiol and (−)Δ9-tetrahydrocannabinol are neuroprotective antioxidants |journal=Proc Natl Acad Sci USA |volume=95 |issue=14 |pages=8268–8273|doi=10.1073/pnas.95.14.8268 |pmid=9653176 |pmc=20965 |doi-access=free }}</ref><ref>{{Cite journal |last=Hampson |first=Aidan J. |date=2006 |title=Neuroprotective Antioxidants from Marijuana |url=https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2000.tb06193.x |journal=Annals of the New York Academy of Sciences |volume=899 |issue=1 |pages=274–282|doi=10.1111/j.1749-6632.2000.tb06193.x |s2cid=39496546 }}</ref>

==See also==
{{Columns-list|colwidth=16em|
* [[Adenosine monophosphate]]
* [[Ajinomoto]]
* [[Disodium glutamate]]
* [[Disodium inosinate]]
* [[Glutamate flavoring]]
* [[Guanosine monophosphate]]
* [[Inosinic acid]]
* [[Kainic acid]]
* [[Monopotassium glutamate]]
* [[Tien Chu Ve-Tsin]]
}}

== References ==
{{Reflist}}

== Further reading ==
{{Commons category|Glutamic acid}}
* {{Lehninger4th}}

==External links==
{{wiktionary}}
* [http://gmd.mpimp-golm.mpg.de/Spectrums/3d091503-3702-4e68-8a71-6754c084f0f9.aspx Glutamic acid MS Spectrum]

{{Digestives}}
{{Amino acids}}
{{Glutamate receptor modulators}}
{{Glutamate metabolism and transport modulators}}
{{Amino acid metabolism intermediates}}
{{Neurotransmitters}}
{{Neurotoxins}}
{{Authority control}}

{{DEFAULTSORT:Glutamic Acid}}
[[Category:Amino acids]]
[[Category:Proteinogenic amino acids]]
[[Category:Glucogenic amino acids]]
[[Category:Excitatory amino acids]]
[[Category:Flavor enhancers]]
[[Category:Umami enhancers]]
[[Category:Glutamates]]
[[Category:Glutamic acids]]
[[Category:Excitatory amino acid receptor agonists]]
[[Category:Glycine receptor agonists]]
[[Category:Peripherally selective drugs]]
[[Category:Chelating agents]]
[[Category:Glutamate (neurotransmitter)]]
[[Category:E-number additives]]