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Glutamic acid
Glutamic acid
(symbol Glu or E[4]) is an α-amino acid with formula C 5H 9O 4N. Its molecular structure could be idealized as HOOC-CH(NH 2)-(CH 2)2-COOH, with two carboxyl groups -COOH and one amino group -NH 2. However, in the solid state and mildly acid water solutions, the molecule assumes an electrically neutral zwitterion structure −OOC-CH(NH+ 3)-(CH 2)2-COOH. The acid can lose one proton from its second carboxyl group to form the conjugate base, the singly-negative anion glutamate −OOC-CH(NH+ 3)-(CH 2)2-COO−. This form of the compound is prevalent in neutral solutions. The glutamate neurotransmitter plays the principal role in neural activation.[5] This anion is also responsible for the savory flavor (umami) of certain foods, and used in glutamate flavorings such as MSG. In highly alkaline solutions the doubly negative anion −OOC-CH(NH 2)-(CH 2)2-COO− prevails. The radical corresponding to glutamate is called glutamyl. Glutamic acid
Glutamic acid
is used by almost all living beings in the biosynthesis of proteins, being specified in DNA
DNA
by the codons GAA or GAG. It is non-essential in humans, meaning the body can synthesize it.

Contents

1 Chemistry

1.1 Ionization 1.2 Optical isomerism

2 History 3 Synthesis

3.1 Biosynthesis 3.2 Industrial synthesis

4 Function and uses

4.1 Metabolism 4.2 Neurotransmitter 4.3 Brain nonsynaptic glutamatergic signaling circuits

4.3.1 GABA precursor

4.4 Flavor enhancer 4.5 Nutrient 4.6 Plant growth 4.7 NMR spectroscopy

5 Pharmacology 6 See also 7 References 8 Further reading 9 External links

Chemistry[edit] Ionization[edit]

The glutamate monoanion.

When glutamic acid is dissolved in water, the amino group (-NH 2) may gain a proton (H+), and/or the carboxyl groups may lose protons, depending on the acidity of the medium. In sufficiently acidic environments, the amino group gains a proton and the molecule becomes a cation with a single positive charge, HOOC-CH(NH+ 3)-(CH 2)2-COOH.[6] At pH values between about 2.5 and 4.1,[6] the carboxylic acid closer to the amine generally loses a proton, and the acid becomes the neutral zwitterion −OOC-CH(NH+ 3)-(CH 2)2-COOH. This is also the form of the compound in the crystalline solid state.[7][8] The change in protonation state is gradual; the two forms are in equal concentrations at pH 2.10.[9] At even higher pH, the other carboxylic acid group loses its proton and the acid exists almost entirely as the glutamate anion −OOC-CH(NH+ 3)-(CH 2)2-COO−, with a single negative charge overall. The change in protonation state occurs at pH 4.07.[9] 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 −OOC-CH(NH 2)-(CH 2)2-COO−. The change in protonation state occurs at pH 9.47.[9] Optical isomerism[edit] The carbon atom adjacent to the amino group is chiral (connected to four distinct groups), so glutamic acid can exist in two optical isomers, D(-) and L(+). The L form is the one most widely occurring in nature, but the D form occurs in some special contexts, such as the cell walls of the bacteria (which can manufacture it from the L form with the enzyme glutamate racemase) and the liver of mammals.[10][11] History[edit] Main article: Glutamic acid
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 twentieth 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.[12] In 1908 Japanese researcher Kikunae Ikeda of the Tokyo Imperial University
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 ineffable but undeniable 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.[13][14] Synthesis[edit] Biosynthesis[edit]

Reactants Products Enzymes

Glutamine
Glutamine
+ H2O → Glu + NH3 GLS, GLS2

NAcGlu + H2O → Glu + Acetate N-acetyl-glutamate synthase

α-ketoglutarate + NADPH + NH4+ → Glu + NADP+ + H2O GLUD1, GLUD2[15]

α-ketoglutarate + α-amino acid → Glu + α-keto acid transaminase

1-Pyrroline-5-carboxylate
1-Pyrroline-5-carboxylate
+ NAD+ + H2O → Glu + NADH ALDH4A1

N-formimino-L-glutamate
N-formimino-L-glutamate
+ FH4 → Glu + 5-formimino-FH4 FTCD

NAAG → Glu + NAA GCPII

Industrial synthesis[edit] Glutamic acid
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.[16] 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.[17] Isolation and purification can be achieved by concentration and crystallization; it is also widely available as its hydrochloride salt.[18] Function and uses[edit] Metabolism[edit] Glutamate
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-ketoacid, typically catalysed by a transaminase. The reaction can be generalised as such:

R1-amino acid + R2-α-ketoacid ⇌ R1-α-ketoacid + R2-amino acid

A very common α-keto acid is α-ketoglutarate, an intermediate in the citric acid cycle. Transamination
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
Alanine
+ α-ketoglutarate ⇌ pyruvate + glutamate

Aspartate
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
Glutamate
also plays an important role in the body's disposal of excess or waste nitrogen. Glutamate
Glutamate
undergoes deamination, an oxidative reaction catalysed by glutamate dehydrogenase,[15] as follows:

glutamate + H2O + NADP+ → α-ketoglutarate + NADPH + NH3 + H+

Ammonia
Ammonia
(as ammonium) is then excreted predominantly as urea, synthesised in the liver. Transamination
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
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.[19][20] Neurotransmitter[edit] Main article: Glutamate
Glutamate
(neurotransmitter) Glutamate
Glutamate
is the most abundant excitatory neurotransmitter in the vertebrate nervous system.[21] At chemical synapses, glutamate is stored in vesicles. Nerve impulses
Nerve impulses
trigger release of glutamate from the presynaptic cell. Glutamate
Glutamate
acts on ionotropic and metabotropic (G-protein coupled) receptors.[21] In the opposing postsynaptic cell, glutamate receptors, such as the NMDA receptor
NMDA receptor
or the AMPA
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.[22] 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
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.[23] In addition, glutamate plays important roles in the regulation of growth cones and synaptogenesis during brain development as originally described by Mark Mattson. Brain nonsynaptic glutamatergic signaling circuits[edit] Extracellular glutamate in Drosophila
Drosophila
brains has been found to regulate postsynaptic glutamate receptor clustering, via a process involving receptor desensitization.[24] A gene expressed in glial cells actively transports glutamate into the extracellular space,[24] while, in the nucleus accumbens-stimulating group II metabotropic glutamate receptors, this gene was found to reduce extracellular glutamate levels.[25] This raises the possibility that this extracellular glutamate plays an "endocrine-like" role as part of a larger homeostatic system. GABA precursor[edit] Glutamate
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), which is most abundant in the cerebellum and pancreas. 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. Flavor enhancer[edit] Main article: Glutamic acid
Glutamic acid
(flavor) 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 and soy sauce, and is responsible for umami, one of the five basic tastes of the human sense of taste. Glutamic acid
Glutamic acid
is often used as a food additive and flavor enhancer in the form of its sodium salt, known as monosodium glutamate (MSG). Nutrient[edit] 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.[26] Plant growth[edit] Auxigro is a plant growth preparation that contains 30% glutamic acid. NMR spectroscopy[edit] In recent years, 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.[27] Pharmacology[edit] The drug phencyclidine (more commonly known as PCP) antagonizes glutamic acid non-competitively at the NMDA receptor. For the same reasons, dextromethorphan and ketamine also have strong dissociative and hallucinogenic effects. Acute infusion of the drug LY354740 (also known as eglumegad, an agonist of the metabotropic glutamate receptors 2 and 3) resulted in a marked diminution of yohimbine-induced stress response in bonnet macaques (Macaca radiata); chronic oral administration of LY354740 in those animals led to markedly reduced baseline cortisol levels (approximately 50 percent) in comparison to untreated control subjects.[28] LY354740 has also been demonstrated to act on the metabotropic glutamate receptor 3 (GRM3) of human adrenocortical cells, downregulating aldosterone synthase, CYP11B1, and the production of adrenal steroids (i.e. aldosterone and cortisol).[29] Glutamate
Glutamate
does not easily pass the blood brain barrier, but, instead, is transported by a high-affinity transport system.[30][31] It can also be converted into glutamine. See also[edit]

Disodium glutamate Kainic acid Monosodium glutamate

References[edit]

^ "L- Glutamic acid
Glutamic acid
CAS#: 56-86-0". www.chemicalbook.com.  ^ Belitz, H.-D; Grosch, Werner; Schieberle, Peter (2009-02-27). "Food Chemistry". ISBN 9783540699330.  ^ "Amino Acid
Acid
Structures". cem.msu.edu. Archived from the original on 1998-02-11.  ^ "Nomenclature and Symbolism for Amino Acids and Peptides". IUPAC-IUB Joint Commission on Biochemical Nomenclature. 1983. Archived from the original on 9 October 2008. Retrieved 5 March 2018.  ^ Robert Sapolsky (2005), Biology and Human Behavior: The Neurological Origins of Individuality (2nd edition); The Teaching Company. Pages 19 and 20 of the Guide Book ^ a b Albert Neuberger (1936), "Dissociation constants and structures of glutamic acid and its esters". Biochemical Journal, volume 30, issue 11, article CCXCIII; pages 2085-2094. PMC 1263308. ^ Rodante, F.; Marrosu, G. (1989). "Thermodynamics of the second proton dissociation processes of nine α-amino-acids and the third ionization processes of glutamic acid, aspartic acid and tyrosine". Thermochimica Acta. 141: 297–303. doi:10.1016/0040-6031(89)87065-0.  ^ Lehmann, Mogens S.; Koetzle, Thomas F.; Hamilton, Walter C. (1972). "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 of Crystal and Molecular Structure. 2 (5): 225–233. doi:10.1007/BF01246639.  ^ a b c William H. Brown and Lawrence S. Brown (2008), Organic Chemistry (5th edition). Cengage Learning. Page 1041. ISBN 0495388572, 9780495388579. ^ National Center for Biotechnology Information, "D-glutamate". PubChem Compound Database, CID=23327. Accessed 2017-02-17. ^ Liu, L; Yoshimura, T; Endo, K; Kishimoto, K; Fuchikami, Y; Manning, JM; Esaki, N; Soda, K (1998). "Compensation for D-glutamate auxotrophy of Escherichia coli WM335 by D-amino acid aminotransferase gene and regulation of murI expression". Bioscience, Biotechnology, and Biochemistry. 62 (1): 193–195. doi:10.1271/bbb.62.193. PMID 9501533.  ^ R.H.A. Plimmer (1912) [1908]. R.H.A. Plimmer; F.G. Hopkins, eds. The Chemical Constitution of the Protein. Monographs on biochemistry. Part I. Analysis (2nd ed.). London: Longmans, Green and Co. p. 114. Retrieved June 3, 2012.  ^ Renton, Alex (2005-07-10). "If MSG is so bad for you, why doesn't everyone in Asia have a headache?". The Guardian. Retrieved 2008-11-21.  ^ " Kikunae Ikeda Sodium Glutamate". Japan Patent Office. 2002-10-07. Retrieved 2008-11-21.  ^ a b Grabowska, A.; Nowicki, M.; Kwinta, J. (2011). "Glutamate dehydrogenase of the germinating triticale seeds: Gene expression, activity distribution and kinetic characteristics". Acta Physiologiae Plantarum. 33 (5): 1981–1990. doi:10.1007/s11738-011-0801-1.  ^ Alvise Perosa; Fulvio Zecchini (25 May 2007). Methods and Reagents for Green Chemistry: An Introduction. John Wiley & Sons. p. 25. ISBN 978-0-470-12407-9.  ^ Michael C. Flickinger (5 April 2010). Encyclopedia of Industrial Biotechnology: Bioprocess, Bioseparation, and Cell Technology, 7 Volume Set. Wiley. pp. 215–225. ISBN 978-0-471-79930-6.  ^ Foley, Patrick; Kermanshahi pour, Azadeh; Beach, Evan S.; Zimmerman, Julie B. (2012). "Derivation and synthesis of renewable surfactants". Chem. Soc. Rev. 41 (4): 1499–1518. doi:10.1039/C1CS15217C. ISSN 0306-0012.  ^ van Lith, SA; Navis, AC; Verrijp, K; Niclou, SP; Bjerkvig, R; Wesseling, P; Tops, B; Molenaar, R; van Noorden, CJ; Leenders, WP (August 2014). " Glutamate
Glutamate
as chemotactic fuel for diffuse glioma cells: are they glutamate suckers?". Biochimica et Biophysica Acta. 1846 (1): 66–74. doi:10.1016/j.bbcan.2014.04.004. PMID 24747768.  ^ van Lith, SA; Molenaar, R; van Noorden, CJ; Leenders, WP (December 2014). "Tumor cells in search for glutamate: an alternative explanation for increased invasiveness of IDH1 mutant gliomas". Neuro-oncology. 16 (12): 1669–70. doi:10.1093/neuonc/nou152. PMC 4232089 . PMID 25074540.  ^ a b Meldrum, B. S. (2000). " Glutamate
Glutamate
as a neurotransmitter in the brain: Review of physiology and pathology". The Journal of Nutrition. 130 (4S Suppl): 1007S–1015S. doi:10.1093/jn/130.4.1007s. PMID 10736372.  ^ 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): 6526–6531. doi:10.1073/pnas.0913154107. PMC 2851965 . PMID 20308566.  ^ a b Augustin H, Grosjean Y, Chen K, Sheng Q, Featherstone DE (2007). "Nonvesicular Release of Glutamate
Glutamate
by Glial xCT Transporters Suppresses Glutamate
Glutamate
Receptor Clustering In Vivo". Journal of Neuroscience. 27 (1): 111–123. doi:10.1523/JNEUROSCI.4770-06.2007. PMC 2193629 . PMID 17202478.  ^ Zheng Xi; Baker DA; Shen H; Carson DS; Kalivas PW (2002). "Group II metabotropic glutamate receptors modulate extracellular glutamate in the nucleus accumbens". Journal of Pharmacology and Experimental Therapeutics. 300 (1): 162–171. doi:10.1124/jpet.300.1.162. PMID 11752112.  ^ Reeds, P.J.; et al. (1 April 2000). "Intestinal glutamate metabolism". Journal of Nutrition. 130 (4s): 978S–982S. PMID 10736365.  ^ C. M. Thiele, Concepts Magn. Reson. A, 2007, 30A, 65-80 ^ Coplan JD, Mathew SJ, Smith EL, Trost RC, Scharf BA, Martinez J, Gorman JM, Monn JA, Schoepp DD, Rosenblum LA (July 2001). "Effects of LY354740, a novel glutamatergic metabotropic agonist, on nonhuman primate hypothalamic-pituitary-adrenal axis and noradrenergic function". CNS Spectr. 6 (7): 607–12, 617. PMID 15573025.  ^ 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 (January 2014). " Glutamate receptors
Glutamate receptors
and the regulation of steroidogenesis in the human adrenal gland: The metabotropic pathway". Molecular and Cellular Endocrinology. 382 (1): 170–177. doi:10.1016/j.mce.2013.09.025. PMID 24080311.  ^ Smith, Quentin R. (April 2000). "Transport of glutamate and other amino acids at the blood–brain barrier". The Journal of Nutrition. American Society for Nutrition. 130 (4S Suppl): 1016S–1022S. PMID 10736373.  ^ Hawkins, Richard A. (September 2009). "The blood-brain barrier and glutamate". The American Journal of Clinical Nutrition. American Society for Nutrition. 90 (3): 867S–874S. doi:10.3945/ajcn.2009.27462BB. Retrieved 2016-07-25. 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. 

Further reading[edit]

Wikimedia Commons has media related to Glutamic acid.

Nelson, David L.; Cox, Michael M. (2005), Principles of Biochemistry (4th ed.), New York: W. H. Freeman, ISBN 0-7167-4339-6 

External links[edit]

Look up glutamic acid in Wiktionary, the free dictionary.

Glutamic acid
Glutamic acid
MS Spectrum

v t e

Digestives, including enzymes (A09)

Enzymes

Diastase Pancreatin Pancrelipase Pepsin

Acid
Acid
preparations

Citric acid Hydrochloric acid

v t e

The encoded amino acid

General topics

Protein Peptide Genetic code

By properties

Aliphatic

Branched-chain amino acids (Valine Isoleucine Leucine) Methionine Alanine Proline Glycine

Aromatic

Phenylalanine Tyrosine Tryptophan Histidine

Polar, uncharged

Asparagine Glutamine Serine Threonine

Positive charge (pKa)

Lysine
Lysine
(≈10.8) Arginine
Arginine
(≈12.5) Histidine
Histidine
(≈6.1)

Negative charge (pKa)

Aspartic acid
Aspartic acid
(≈3.9) Glutamic acid
Glutamic acid
(≈4.1) Cysteine
Cysteine
(≈8.3) Tyrosine
Tyrosine
(≈10.1)

Amino acids
Amino acids
types: Encoded (proteins) Essential Non-proteinogenic Ketogenic Glucogenic Imino acids D-amino acids Dehydroamino acids

Glutamate receptor
Glutamate receptor
modulators

v t e

Ionotropic glutamate receptor
Ionotropic glutamate receptor
modulators

AMPAR

Agonists: Main site agonists: 5-Fluorowillardiine Acromelic acid (acromelate) AMPA BOAA Domoic acid Glutamate Ibotenic acid Proline Quisqualic acid Willardiine; Positive allosteric modulators: Aniracetam Cyclothiazide CX-516 CX-546 CX-614 Farampator
Farampator
(CX-691, ORG-24448) CX-717 CX-1739 CX-1942 Diazoxide Hydrochlorothiazide
Hydrochlorothiazide
(HCTZ) IDRA-21 LY-392098 LY-395153 LY-404187 LY-451646 LY-503430 Mibampator
Mibampator
(LY-451395) Nooglutyl ORG-26576 Oxiracetam PEPA PF-04958242 Piracetam Pramiracetam S-18986 Tulrampator
Tulrampator
(S-47445, CX-1632)

Antagonists: ACEA-1011 ATPO Becampanel Caroverine CNQX Dasolampanel DNQX Fanapanel
Fanapanel
(MPQX) GAMS Kaitocephalin Kynurenic acid Kynurenine Licostinel
Licostinel
(ACEA-1021) NBQX PNQX Selurampanel Tezampanel Theanine Topiramate YM90K Zonampanel; Negative allosteric modulators: Barbiturates
Barbiturates
(e.g., pentobarbital, sodium thiopental) Cyclopropane Enflurane Ethanol (alcohol) Evans blue GYKI-52466 GYKI-53655 Halothane Irampanel Isoflurane Perampanel Pregnenolone sulfate Sevoflurane Talampanel; Unknown/unsorted antagonists: Minocycline

KAR

Agonists: Main site agonists: 5-Bromowillardiine 5-Iodowillardiine Acromelic acid (acromelate) AMPA ATPA Domoic acid Glutamate Ibotenic acid Kainic acid LY-339434 Proline Quisqualic acid SYM-2081; Positive allosteric modulators: Cyclothiazide Diazoxide Enflurane Halothane Isoflurane

Antagonists: ACEA-1011 CNQX Dasolampanel DNQX GAMS Kaitocephalin Kynurenic acid Licostinel
Licostinel
(ACEA-1021) LY-382884 NBQX NS102 Selurampanel Tezampanel Theanine Topiramate UBP-302; Negative allosteric modulators: Barbiturates
Barbiturates
(e.g., pentobarbital, sodium thiopental) Enflurane Ethanol (alcohol) Evans blue NS-3763 Pregnenolone sulfate

NMDAR

Agonists: Main site agonists: AMAA Aspartate Glutamate Homocysteic acid
Homocysteic acid
(L-HCA) Homoquinolinic acid Ibotenic acid NMDA Proline Quinolinic acid Tetrazolylglycine Theanine; Glycine
Glycine
site agonists: β-Fluoro-D-alanine ACBD ACC (ACPC) ACPD AK-51 Apimostinel
Apimostinel
(NRX-1074) B6B21 CCG D-Alanine D-Cycloserine D-Serine DHPG Dimethylglycine Glycine HA-966 L-687414 L-Alanine L-Serine Milacemide Neboglamine
Neboglamine
(nebostinel) Rapastinel
Rapastinel
(GLYX-13) Sarcosine; Polyamine site agonists: Neomycin Spermidine Spermine; Other positive allosteric modulators: 24S-Hydroxycholesterol DHEA (prasterone) DHEA sulfate
DHEA sulfate
(prasterone sulfate) Epipregnanolone sulfate Pregnenolone sulfate SAGE-201 SAGE-301 SAGE-718

Antagonists: Competitive antagonists: AP5
AP5
(APV) AP7 CGP-37849 CGP-39551 CGP-39653 CGP-40116 CGS-19755 CPP Kaitocephalin LY-233053 LY-235959 LY-274614 MDL-100453 Midafotel
Midafotel
(d-CPPene) NPC-12626 NPC-17742 PBPD PEAQX Perzinfotel PPDA SDZ-220581 Selfotel; Glycine
Glycine
site antagonists: 4-Cl-KYN (AV-101) 5,7-DCKA 7-CKA ACC ACEA-1011 ACEA-1328 Apimostinel
Apimostinel
(NRX-1074) AV-101 Carisoprodol CGP-39653 CNQX D-Cycloserine DNQX Felbamate Gavestinel GV-196771 Harkoseride Kynurenic acid Kynurenine L-689560 L-701324 Licostinel
Licostinel
(ACEA-1021) LU-73068 MDL-105519 Meprobamate MRZ 2/576 PNQX Rapastinel
Rapastinel
(GLYX-13) ZD-9379; Polyamine site antagonists: Arcaine Co 101676 Diaminopropane Diethylenetriamine Huperzine A Putrescine; Uncompetitive pore blockers (mostly dizocilpine site): 2-MDP 3-HO-PCP 3-MeO-PCE 3-MeO-PCMo 3-MeO-PCP 4-MeO-PCP 8A-PDHQ 18-MC α-Endopsychosin Alaproclate Alazocine
Alazocine
(SKF-10047) Amantadine Aptiganel Argiotoxin-636 Arketamine ARL-12495 ARL-15896-AR ARL-16247 Budipine Coronaridine Delucemine
Delucemine
(NPS-1506) Dexoxadrol Dextrallorphan Dextromethadone Dextromethorphan Dextrorphan Dieticyclidine Diphenidine Dizocilpine Ephenidine Esketamine Etoxadrol Eticyclidine Fluorolintane Gacyclidine Ibogaine Ibogamine Indantadol Ketamine Ketobemidone Lanicemine Levomethadone Levomethorphan Levomilnacipran Levorphanol Loperamide Memantine Methadone Methorphan Methoxetamine Methoxphenidine Milnacipran Morphanol NEFA Neramexane Nitromemantine Noribogaine Norketamine Orphenadrine PCPr PD-137889 Pethidine
Pethidine
(meperidine) Phencyclamine Phencyclidine Propoxyphene Remacemide Rhynchophylline Rimantadine Rolicyclidine Sabeluzole Tabernanthine Tenocyclidine Tiletamine Tramadol; Ifenprodil (NR2B) site antagonists: Besonprodil Buphenine
Buphenine
(nylidrin) CO-101244 (PD-174494) Eliprodil Haloperidol Isoxsuprine Radiprodil (RGH-896) Rislenemdaz
Rislenemdaz
(CERC-301, MK-0657) Ro 8-4304 Ro 25-6981 Safaprodil Traxoprodil
Traxoprodil
(CP-101606); NR2A-selective antagonists: MPX-004 MPX-007 TCN-201 TCN-213; Cations: Hydrogen Magnesium Zinc; Alcohols/volatile anesthetics/related: Benzene Butane Chloroform Cyclopropane Desflurane Diethyl ether Enflurane Ethanol (alcohol) Halothane Hexanol Isoflurane Methoxyflurane Nitrous oxide Octanol Sevoflurane Toluene Trichloroethane Trichloroethanol Trichloroethylene Urethane Xenon Xylene; Unknown/unsorted antagonists: ARR-15896 Bumetanide Caroverine Conantokin D-αAA Dexanabinol Flufenamic acid Flupirtine FPL-12495 FR-115427 Furosemide Hodgkinsine Ipenoxazone (MLV-6976) MDL-27266 Metaphit Minocycline MPEP Niflumic acid Pentamidine Pentamidine
Pentamidine
isethionate Piretanide Psychotridine Transcrocetin
Transcrocetin
(saffron)

See also: Receptor/signaling modulators Metabotropic glutamate receptor
Metabotropic glutamate receptor
modulators Glutamate
Glutamate
metabolism/transport modulators

v t e

Metabotropic glutamate receptor
Metabotropic glutamate receptor
modulators

Group I

mGluR1

Agonists: ACPD DHPG Glutamate Ibotenic acid Quisqualic acid Ro01-6128 Ro67-4853 Ro67-7476 VU-71 Theanine

Antagonists: BAY 36-7620 CPCCOEt Cyclothiazide LY-367,385 LY-456,236 MCPG NPS-2390

mGluR5

Agonists: ACPD ADX-47273 CDPPB CHPG DFB DHPG Glutamate Ibotenic acid Quisqualic acid VU-1545

Antagonists: CTEP DMeOB LY-344,545 Mavoglurant MCPG NPS-2390 Remeglurant SIB-1757 SIB-1893; Negative allosteric modulators: Basimglurant Dipraglurant Fenobam GRN-529 MPEP MTEP Raseglurant

Group II

mGluR2

Agonists: BINA CBiPES DCG-IV Eglumegad Glutamate Ibotenic acid LY-379,268 LY-404,039
LY-404,039
(pomaglumetad) LY-487,379 LY-566,332 MGS-0028 Pomaglumetad methionil (LY-2140023) Talaglumetad; Positive allosteric modulators: JNJ-40411813
JNJ-40411813
(ADX-71149)

Antagonists: APICA CECXG EGLU HYDIA LY-307,452 LY-341,495 MCPG MGS-0039 PCCG-4; Negative allosteric modulators: Decoglurant RO4491533

mGluR3

Agonists: CBiPES DCG-IV Eglumegad Glutamate Ibotenic acid LY-379,268 LY-404,039
LY-404,039
(pomaglumetad) LY-487,379 MGS-0028 Pomaglumetad methionil (LY-2140023) Talaglumetad

Antagonists: APICA CECXG EGLU HYDIA LY-307,452 LY-341,495 MCPG MGS-0039; Negative allosteric modulators: Decoglurant RO4491533

Group III

mGluR4

Agonists: Glutamate L-AP4 PHCCC VU-001,171 VU-0155,041; Positive allosteric modulators: Foliglurax MPEP

Antagonists: CPPG MAP4 MPPG MSOP MTPG UBP-1112

mGluR6

Agonists: Glutamate L-AP4

Antagonists: CPPG MAP4 MPPG MSOP MTPG UBP-1112

mGluR7

Agonists: AMN082 Glutamate L-AP4

Antagonists: CPPG MAP4 MMPIP MPPG MSOP MTPG UBP-1112

mGluR8

Agonists: DCPG Glutamate L-AP4

Antagonists: CPPG MAP4 MPPG MSOP MTPG UBP-1112

See also: Receptor/signaling modulators • Ionotropic glutamate receptor modulators • Glutamate
Glutamate
metabolism/transport modulators

v t e

Glutamate
Glutamate
metabolism and transport modulators

Transporter

EAATs

Amphetamine Aspartic acid
Aspartic acid
(aspartate) cis-ACBD DHKA Glutamic acid
Glutamic acid
(glutamate) HIP-A HIP-B Kainic acid L-(-)-threo-3-Hydroxyaspartic acid L-αAA L-CCG-III ((2S,3S,4R)-CCG) L-Serine-O-sulphate (SOS) L-trans-2,4-PDC MPDC Maslinic acid SYM-2081 TBOA TFB-TBOA Theanine threo-3-Methylglutamic acid UCPH-101 WAY-213,613

vGluTs

4-Methylene-L-glutamate 6-(4'-Phenylstyryl)-QDC 6-Biphenyl-4-yl-QDC 7-CKA Acid
Acid
red 114 Amido black 10B
Amido black 10B
(naphthol blue black) Bafilomycin A1 Benzopurpurin 4B Bumetamide Chicago sky blue 6B Aspartic acid
Aspartic acid
(aspartate) DIDS Direct blue 71 Erythro-4-methyl-L-glutamic acid Evans blue Furosemide Glutamic acid
Glutamic acid
(glutamate) Kynurenic acid Nigericin NPPB (N144) Ponceau SS Reactive blue 2 Rose bengal SITS trans-ACDP Trypan blue Valinomycin Xanthurenic acid

Enzyme

GAH

BPTES CB-839 DON

AST

2-Amino-3-butenoic acid AAOA AMB β-DL-Methylene-aspartate Hydrazinosuccinate

ALT

β-Chloro-L-alanine L-Cycloserine Propargylglycine

GDH

AAOA Bithionol Chloroquine EGCG GTP GW5074 Hexachlorophene Hydroxylamine Palmitoyl-CoA Pyridoxal phosphate

GS

2-Aminoadipic acid JFD01307SC Methionine
Methionine
sulfoximine Phosphinothricin
Phosphinothricin
(glufosinate)

GAD

3-Mercaptopropionic acid AAOA L-Allylglycine Semicarbazide

See also: Receptor/signaling modulators • Ionotropic glutamate receptor modulators • Metabotropic glutamate receptor
Metabotropic glutamate receptor
modulators • GABA metabolism and transport modulators

v t e

Amino acid
Amino acid
metabolism metabolic intermediates

K→acetyl-CoA

lysine→

Saccharopine Allysine α-Aminoadipic acid α-Ketoadipate Glutaryl-CoA Glutaconyl-CoA Crotonyl-CoA β-Hydroxybutyryl-CoA

leucine→

β-Hydroxy β-methylbutyric acid β-Hydroxy β-methylbutyryl-CoA Isovaleryl-CoA α-Ketoisocaproic acid β-Ketoisocaproic acid β-Ketoisocaproyl-CoA β-Leucine β-Methylcrotonyl-CoA β-Methylglutaconyl-CoA β-Hydroxy β-methylglutaryl-CoA

tryptophan→alanine→

N'-Formylkynurenine Kynurenine Anthranilic acid 3-Hydroxykynurenine 3-Hydroxyanthranilic acid 2-Amino-3-carboxymuconic semialdehyde 2-Aminomuconic semialdehyde 2-Aminomuconic acid Glutaryl-CoA

G

G→pyruvate→citrate

glycine→serine→

3-Phosphoglyceric acid

glycine→creatine: Glycocyamine Phosphocreatine Creatinine

G→glutamate→ α-ketoglutarate

histidine→

Urocanic acid Imidazol-4-one-5-propionic acid Formiminoglutamic acid Glutamate-1-semialdehyde

proline→

1-Pyrroline-5-carboxylic acid

arginine→

Agmatine Ornithine Citrulline Cadaverine Putrescine

other

cysteine+glutamate→glutathione: γ-Glutamylcysteine

G→propionyl-CoA→ succinyl-CoA

valine→

α-Ketoisovaleric acid Isobutyryl-CoA Methacrylyl-CoA 3-Hydroxyisobutyryl-CoA 3-Hydroxyisobutyric acid 2-Methyl-3-oxopropanoic acid

isoleucine→

2,3-Dihydroxy-3-methylpentanoic acid 2-Methylbutyryl-CoA Tiglyl-CoA 2-Methylacetoacetyl-CoA

methionine→

generation of homocysteine: S-Adenosyl methionine S-Adenosyl-L-homocysteine Homocysteine

conversion to cysteine: Cystathionine alpha-Ketobutyric acid+Cysteine

threonine→

α-Ketobutyric acid

propionyl-CoA→

Methylmalonyl-CoA

G→fumarate

phenylalanine→tyrosine→

4-Hydroxyphenylpyruvic acid Homogentisic acid 4-Maleylacetoacetic acid

G→oxaloacetate

see urea cycle

Other

Cysteine
Cysteine
metabolism

Cysteine
Cysteine
sulfinic acid

v t e

Neurotransmitters

Amino acid-derived

Major excitatory/inhibitory systems: Glutamate
Glutamate
system: Agmatine Aspartic acid
Aspartic acid
(aspartate) Cycloserine Glutamic acid
Glutamic acid
(glutamate) Glutathione Glycine GSNO GSSG Kynurenic acid NAA NAAG Proline Serine; GABA system: GABA GABOB GHB; Glycine
Glycine
system: α-Alanine β-Alanine Glycine Hypotaurine Proline Sarcosine Serine Taurine; GHB system: GHB T-HCA (GHC)

Biogenic amines: Monoamines: 6-OHM Dopamine Epinephrine
Epinephrine
(adrenaline) NAS (normelatonin) Norepinephrine
Norepinephrine
(noradrenaline) Serotonin
Serotonin
(5-HT); Trace amines: 3-Iodothyronamine N-Methylphenethylamine N-Methyltryptamine m-Octopamine p-Octopamine Phenylethanolamine Phenethylamine Synephrine Tryptamine m-Tyramine p-Tyramine; Others: Histamine

Neuropeptides: See here instead.

Lipid-derived

Endocannabinoids: 2-AG 2-AGE (noladin ether) 2-ALPI 2-OG AA-5-HT Anandamide
Anandamide
(AEA) DEA LPI NADA NAGly OEA Oleamide PEA RVD-Hpα SEA Virodhamine
Virodhamine
(O-AEA)

Neurosteroids: See here instead.

Nucleobase-derived

Nucleosides: Adenosine
Adenosine
system: Adenosine ADP AMP ATP

Vitamin-derived

Cholinergic system: Acetylcholine

Miscellaneous

Gasotransmitters: Carbon
Carbon
monoxide (CO) Hydrogen
Hydrogen
sulfide (H2S) Nitric oxide
Nitric oxide
(NO); Candidates: Acetaldehyde Ammonia
Ammonia
(NH3) Carbonyl sulfide
Carbonyl sulfide
(COS) Nitrous oxide
Nitrous oxide
(N2O) Sulfur dioxide
Sulfur dioxide
(SO2)

v t e

Neurotoxins

Animal

Batrachotoxin Bestoxin Birtoxin Bungarotoxin Charybdotoxin Conotoxin Fasciculin Huwentoxin Poneratoxin Saxitoxin Tetrodotoxin Vanillotoxin Spooky toxin (SsTx)

Bacterial

Botulinum toxin Tetanospasmin

Cyanobacteria

Anatoxin-a Anatoxin-a(S) BMAA Saxitoxin

Plant

Bicuculline Penitrem A Picrotoxin Strychnine Tutin Rotenone Ginkgotoxin Cicutoxin Oenanthotoxin

Pesticides

Fenpropathrin Tetramethylenedisulfotetramine Bromethalin Crimidine Methamidophos Endosulfan Fipronil

Nerve agents

Cyclosarin EA-3148 Novichok agent Sarin Soman Tabun VE VG VM VR VX GV

Other

Dimethylmercury Toxopyrimidine

Authority control

LCCN: sh85055379 GND: 41137

.