GLUTAMIC ACID is an α-amino acid with formula C
4N. It is usually abbreviated as GLU or E in biochemistry . Its
molecular structure could be idealized as HOOC-CH(NH
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
The acid can lose one proton from its second carboxyl group to form
the conjugate base , the singly-negative anion GLUTAMATE −OOC-CH(NH+
2)2-COO−. This form of the compound is prevalent in neutral
solutions. The glutamate neurotransmitter plays the principal role in
neural activation . 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
2)2-COO− prevails. The radical corresponding to glutamate is called
Glutamic acid is used by almost all living beings in the biosynthesis
of proteins , being specified in
DNA by the codons GAA or GAG. It is
non-essential in humans, meaning the body can synthesize it.
* 1 Chemistry
* 1.1 Ionization
* 1.2 Optical isomerism
* 2 History
* 3 Synthesis
* 3.2 Industrial synthesis
* 4 Function and uses
* 4.3 Brain nonsynaptic glutamatergic signaling circuits
* 4.3.1 GABA precursor
* 4.5 Nutrient
* 4.6 Plant growth
* 5 Pharmacology
* 6 See also
* 7 References
* 8 Further reading
* 9 External links
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,
At pH values between about 2.5 and 4.1., the carboxylic acid closer
to the amine generally loses a proton, and the acid becomes the
neutral zwitterion −OOC-CH(NH+
2)2-COOH. This is also the form of the compound in the crystalline
solid state. The change in protonation state is gradual; the two
forms are in equal concentrations at pH 2.10.
At even higher pH, the other carboxylic acid group loses its proton
and the acid exists almost entirely as the glutamate anion
2)2-COO−, with a single negative charge overall. The change in
protonation state occurs at pH 4.07. This form with both carboxylates
lacking protons is dominant in the physiological pH range
At even higher pH, the amino group loses the extra proton and the
prevalent species is the doubly-negative anion −OOC-CH(NH
2)2-COO−. The change in protonation state occurs at pH 9.47.
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 bacterium
Escherichia coli (which can manufacture it
from the L form with the enzyme glutamate racemase ) and the liver of
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 . 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 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
Glutamine + H2O
→ GLU + NH3
GLS , GLS2
NAcGlu + H2O
→ GLU +
NADP H + NH4+
→ GLU +
NADP + + H2O
GLUD1 , GLUD2
α-ketoglutarate + α-amino acid
→ GLU + α-keto acid
1-Pyrroline-5-carboxylate + NAD+ + H2O
→ GLU + NADH
N-formimino-L-glutamate + FH4
→ GLU + 5-formimino-FH4
→ GLU + NAA
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.
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. Isolation and purification can be achieved by
concentration and crystallization ; it is also widely available as its
FUNCTION AND USES
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 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:
α-ketoglutarate ⇌ pyruvate + glutamate
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
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 , 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 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.
Glutamate is the most abundant excitatory neurotransmitter in the
vertebrate nervous system . At chemical synapses , glutamate is
stored in vesicles .
Nerve impulses trigger release of glutamate from
the presynaptic cell.
Glutamate acts on ionotropic and metabotropic
(G-protein coupled) receptors. In the opposing postsynaptic cell,
glutamate receptors , such as the
NMDA receptor or the
AMPA receptor ,
bind glutamate and are activated. Because of its role in synaptic
plasticity , glutamate is involved in cognitive functions such as
learning and memory in the brain. The form of plasticity known as
long-term potentiation takes place at glutamatergic synapses in the
hippocampus , neocortex , and other parts of the brain. Glutamate
works not only as a point-to-point transmitter, but also through
spill-over synaptic crosstalk between synapses in which summation of
glutamate released from a neighboring synapse creates extrasynaptic
signaling/volume transmission . 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
Extracellular glutamate in
Drosophila brains has been found to
regulate postsynaptic glutamate receptor clustering, via a process
involving receptor desensitization. A gene expressed in glial cells
actively transports glutamate into the extracellular space , while,
in the nucleus accumbens -stimulating group II metabotropic glutamate
receptors, this gene was found to reduce extracellular glutamate
levels. This raises the possibility that this extracellular glutamate
plays an "endocrine-like" role as part of a larger homeostatic system.
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.
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 is often used as a food additive and
flavor enhancer in the form of its sodium salt , known as monosodium
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 the protein in wheat is glutamic acid.
Ninety-five percent of the dietary glutamate is metabolized by
intestinal cells in a first pass.
Auxigro is a plant growth preparation that contains 30% glutamic
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.
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. 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
Glutamate does not easily pass the blood brain barrier ,
but, instead, is transported by a high-affinity transport system. It
can also be converted into glutamine .
* ^ "L-
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 Structures". cem.msu.edu. Archived from the
original on 1998-02-11.
* ^ 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
* ^ A B C William H. Brown and Lawrence S. Brown (2008), Organic
Chemistry (5th edition). Cengage Learning. Page 1041. ISBN 0495388572
* ^ 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
Escherichia coli WM335 by D-amino acid aminotransferase
gene and regulation of murI expression". Bioscience, Biotechnology and
Biochemistry. 62 (1): 193–195. PMID 9501533 . doi
* ^ R.H.A. Plimmer (1912) . 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
* ^ "
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. ISSN 0306-0012 .
doi :10.1039/C1CS15217C .
* ^ 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 as chemotactic fuel for diffuse glioma
cells: are they glutamate suckers?". Biochimica et Biophysica Acta.
1846 (1): 66–74. PMID 24747768 . doi :10.1016/j.bbcan.2014.04.004 .
* ^ 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. PMC 4232089 . PMID 25074540 .
doi :10.1093/neuonc/nou152 .
* ^ A B Meldrum, B. S. (2000). "
Glutamate as a neurotransmitter in
the brain: Review of physiology and pathology". The Journal of
Nutrition. 130 (4S Suppl): 1007S–1015S. PMID 10736372 .
* ^ McEntee, W. J.; Crook, T. H. (1993). "Glutamate: Its role in
learning, memory, and the aging brain". Psychopharmacology. 111 (4):
391–401. PMID 7870979 . doi :10.1007/BF02253527 .
* ^ 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
* ^ A B Augustin H, Grosjean Y, Chen K, Sheng Q, Featherstone DE
(2007). "Nonvesicular Release of
Glutamate by Glial xCT Transporters
Glutamate Receptor Clustering In Vivo" . Journal of
Neuroscience. 27 (1): 111–123. PMC 2193629 . PMID 17202478 . doi
* ^ 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. PMID 11752112 . doi
* ^ Reeds, P.J.; et al. (1 April 2000). "Intestinal glutamate
metabolism". Journal of Nutrition. 130 (4s): 978S–982S. PMID
* ^ 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). "
and the regulation of steroidogenesis in the human adrenal gland: The
metabotropic pathway.". Molecular and Cellular Endocrinology. 382 (1):
170–177. PMID 24080311 . doi :10.1016/j.mce.2013.09.025 .
* ^ Smith, Quentin R. (April 2000). "Transport of glutamate and
other amino acids at the blood–brain barrier". The Journal of
American Society for Nutrition . 130 (4S Suppl):
1016S–1022S. PMID 10736373 .
* ^ Hawkins, Richard A. (September 2009). "The blood-brain barrier
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.
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.
Glutamic acid MS