Glutamic acid

Source: Wikipedia, the free encyclopedia.
Not to be confused with Glutamine or Glutaric acid.
For the anion in its role as a neurotransmitter, see Glutamate (neurotransmitter).

Glutamic acid
Glutamic acid in non ionic form
Glutamic acid in non ionic form
Skeletal formula of L-glutamic acid
Names
IUPAC name
Glutamic acid
Systematic IUPAC name
2-Aminopentanedioic acid
Other names
  • 2-Aminoglutaric acid
Identifiers
  • l isomer: 56-86-0 checkY
  • racemate: 617-65-2 checkY
  • d isomer: 6893-26-1 checkY
3D model (
JSmol
)
1723801 (L) 1723799 (rac) 1723800 (D)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard
 100.009.567 Edit this at Wikidata
EC Number
  • l isomer: 200-293-7
E number E620 (flavour enhancer)
3502 (L) 101971 (rac) 201189 (D)
KEGG
UNII
  • InChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10) checkY
    Key: WHUUTDBJXJRKMK-UHFFFAOYSA-N checkY
  • l isomer: InChI=1/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)
    Key: WHUUTDBJXJRKMK-UHFFFAOYAD
SMILES
  • l isomer: C(CC(=O)O)[C@@H](C(=O)O)N
  • d isomer: C(CC(=O)O)[C@H](C(=O)O)N
  • Zwitterion: C(CC(=O)O)C(C(=O)[O-])[NH3+]
  • Deprotonated zwitterion: C(CC(=O)[O-])C(C(=O)[O-])[NH3+]
Properties
C5H9NO4
Molar mass 147.130 g·mol−1
Appearance White crystalline powder
Density 1.4601 (20 °C)
Melting point 199 °C (390 °F; 472 K) decomposes
8.57 g/L (25 °C)[1]
Solubility Ethanol: 350 μg/100 g (25 °C)[2]
Acidity (pKa) 2.10, 4.07, 9.47[3]
−78.5·10−6 cm3/mol
Hazards
GHS labelling:
GHS07: Exclamation mark
Warning
H315, H319, H335
P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
0
Supplementary data page
Glutamic acid (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Glutamic acid ball and stick model spinning

Glutamic acid (symbol Glu or E;

gamma-aminobutyric acid
(GABA) in GABAergic neurons.

Its molecular formula is C
5H
9NO
4. Glutamic acid exists in two optically isomeric forms; the

codons
GAA or GAG.

The acid can lose one

E620. 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.

The one-letter symbol E for glutamate was assigned as the letter following D for aspartate, as glutamate is larger by one methylene –CH2– group.[7]

Chemistry

Ionization

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, both carboxyl groups are protonated and the molecule becomes a

cation with a single positive charge, HOOC−CH(NH+
3)−(CH
2)2−COOH.[8]

At pH values between about 2.5 and 4.1,[8] 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.[9][10] The change in protonation state is gradual; the two forms are in equal concentrations at pH 2.10.[11]

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.

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.[11]

Optical isomerism

Glutamic acid is

mammals.[12][13]

History

Main article:
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

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.[15][16]

Synthesis

Biosynthesis

Reactants
 Products
Enzymes
glutamine + H2O → Glu + NH3
GLS2
NAcGlu + H2O
 → Glu + acetate N-acetyl-glutamate synthase
NADP
H + NH4+		 → Glu +
NADP
+ + H2O
GLUD2[17]
α-ketoglutarate + α-amino acid
 → Glu + α-keto acid transaminase
1-pyrroline-5-carboxylate + NAD+ + H2O → Glu + NADH
ALDH4A1
FH4
 → Glu +
5-formimino-FH4
FTCD
NAAG → Glu + NAA GCPII

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.[18] 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.[19] Isolation and purification can be achieved by concentration and crystallization; it is also widely available as its hydrochloride salt.[20]

Function and uses

Metabolism

Glutamate is a key compound in cellular

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 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:

pyruvate
+ glutamate
oxaloacetate
+ glutamate

Both

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,[17] as follows:

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

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

IDH1.[21][22]

See also: Glutamate–glutamine cycle

Neurotransmitter

Main article: Glutamate (neurotransmitter)

Glutamate is the most abundant excitatory

brain development as originally described by Mark Mattson
.

Brain nonsynaptic glutamatergic signaling circuits

Extracellular glutamate in

glial cells actively transports glutamate into the extracellular space,[26] while, in the nucleus accumbens-stimulating group II metabotropic glutamate receptors, this gene was found to reduce extracellular glutamate levels.[27]
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).[28] GABA-ergic neurons are identified (for research purposes) by revealing its activity (with the autoradiography and immunohistochemistry methods)[29] which is most abundant in the cerebellum and pancreas.[30]

diabetes mellitus.[31]

Flavor enhancer

Main article: 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

flavor enhancer in the form of its sodium 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.[32]

Plant growth

Auxigro is a plant growth preparation that contains 30% glutamic acid.

NMR spectroscopy

In recent years,[when?] 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.[33]

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.[34]

Pharmacology

The drug

blood brain barrier, but, instead, is transported by a high-affinity transport system.[37][38] It can also be converted into glutamine
.

Glutamate toxicity can be reduced by antioxidants, and the psychoactive principle of cannabis, tetrahydrocannabinol (THC), and the non psychoactive principle cannabidiol (CBD), and other cannabinoids, is found to block glutamate neurotoxicity with a similar potency, and thereby potent antioxidants.[39][40]

See also

References

  1. ^ "L-Glutamic acid". National Library of Medicine. Retrieved 24 June 2023.
  2. ISBN 978-3540699330
    .
  3. ^ "Amino Acid Structures". cem.msu.edu. Archived from the original on 11 February 1998.
  4. ^ "Nomenclature and Symbolism for Amino Acids and Peptides". IUPAC-IUB Joint Commission on Biochemical Nomenclature. 1983. Archived from the original on 29 August 2017. Retrieved 5 March 2018.
  5. ^ Webster's Third New International Dictionary of the English Language Unabridged, Third Edition, 1971.
  6. ^ Robert Sapolsky (2005), Biology and Human Behavior: The Neurological Origins of Individuality (2nd edition); The Teaching Company. pp. 19–20 of the Guide Book.
  7. doi:10.1016/S0307-4412(97)00167-2
    .
  8. ^
    PMID 16746266
    .
  9. doi:10.1016/0040-6031(89)87065-0
    .
  10. S2CID 93590487
    .
  11. ^
    ISBN 0495388572, 978-0495388579
    .
  12. ^ National Center for Biotechnology Information, "D-glutamate". PubChem Compound Database, CID=23327. Accessed 2017-02-17.
  13. PMID 9501533
    .
  14. ^ R. H. A. Plimmer (1912) [1908]. R. H. A. Plimmer; F. G. Hopkins (eds.). The Chemical Constitution of the Protein. Monographs on biochemistry. Vol. Part I. Analysis (2nd ed.). London: Longmans, Green and Co. p. 114. Retrieved 3 June 2012.
  15. ^ Renton, Alex (10 July 2005). "If MSG is so bad for you, why doesn't everyone in Asia have a headache?". The Guardian. Retrieved 21 November 2008.
  16. ^ "Kikunae Ikeda Sodium Glutamate". Japan Patent Office. 7 October 2002. Archived from the original on 28 October 2007. Retrieved 21 November 2008.
  17. ISBN 978-0-470-12407-9
    .
  18. ISBN 978-0-471-79930-6
    .
  19. PMID 22006024
    .
  20. PMID 24747768
    .
  21. PMID 25074540
    .
  22. ^
    PMID 10736372
    .
  23. S2CID 37400348
    .
  24. PMID 20308566
    .
  25. ^
    PMID 17202478
    .
  26. PMID 11752112
    .
  27. PMID 16787421
    .
  28. PMID 7494864
    .
  29. ISBN 978-0-444-52763-9
    .
  30. PMID 35717735
    .
  31. PMID 10736365
    .
  32. ^ C. M. Thiele, Concepts Magn. Reson. A, 2007, 30A, 65–80
  33. PMID 18687554
    .
  34. S2CID 6029856
    .
  35. S2CID 3357749
    .
  36. PMID 10736373
    .
  37. PMID 19571220
    . 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.
  38. PMID 9653176
    .
  39. S2CID 39496546
    .

Further reading

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
    .
Look up glutamic acid in Wiktionary, the free dictionary.