Glutamic acid

Glutamic acid

Names
Systematic IUPAC name 2-Aminopentanedioic acid
Other names 2-Aminoglutaric acid
Identifiers
CAS Number	56-86-0 (L isomer) N 617-65-2 (D/L racemate) N
ChEBI	CHEBI:18237 Y
ChEMBL	ChEMBL276389. N
ChemSpider	591 Y
Jmol interactive 3D	Image
KEGG	D0434 N
UNII	61LJO5I15S Y
InChI InChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10) Y Key: WHUUTDBJXJRKMK-UHFFFAOYSA-N Y 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 C(CC(=O)O)C(C(=O)O)N
Properties
Chemical formula	C5H9NO4
Molar mass	147.13 g·mol−1
Appearance	white crystalline powder
Density	1.4601 (20 °C)
Melting point	199 °C (390 °F; 472 K) decomposes
Solubility in water	7.5 g/L (20 °C)[1]
Solubility	0.00035g/100g ethanol (25 °C)[2]
Acidity (pKa)	2.1, 4.07, 9.47 [3]
Hazards
Safety data sheet	See: data page
NFPA 704	1 2 0
Supplementary data page
Structure and properties	Refractive index (n), Dielectric constant (εr), etc.
Thermodynamic data	Phase behaviour solid–liquid–gas
Spectral data	UV, IR, NMR, MS
N verify (what is YN ?)
Infobox references

Glutamic acid (abbreviated as Glu or E; encoded by the codons GAA or GAG) is an ɑ-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated -+NH3 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated –COO- form under biological conditions), and a side chain carboxylic acid, classifying it as a polar negatively charged (at physiological pH), aliphatic amino acid. It is non-essential in humans, meaning the body can synthesize it.

In neuroscience, its carboxylate anion glutamate is an important excitatory neurotransmitter that plays the principal role in neural activation.^[4]

Chemistry

The side chain carboxylic acid functional group has a pK_a of 4.1 and therefore exists almost entirely in its negatively charged deprotonated carboxylate form at pH values greater than 4.1; therefore, it is negatively charged at physiological pH ranging from 7.35 to 7.45.

History

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.^[5] 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 glutamate.^[6][7]

Biosynthesis

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-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:

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,^[8] 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 mutations become more dependent on glutamate due to mutations in the gene IDH1.^[9][10]

Neurotransmitter

Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system.^[11] 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.^[11] 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.^[12] 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.^[13] 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.^[14] A gene expressed in glial cells actively transports glutamate into the extracellular space,^[14] while, in the nucleus accumbens-stimulating group II metabotropic glutamate receptors, this gene was found to reduce extracellular glutamate levels.^[15] 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), which is most abundant in the cerebellum and pancreas.

Stiff-man 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

Glutamic acid, being a constituent of protein, is present in every food that contains 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 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 the protein in wheat is glutamic acid. Ninety-five percent of the dietary glutamate is metabolized by intestinal cells in a first pass.^[16]

Plant growth

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

NMR spectroscopy

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.^[17]

Pharmacology

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.^[18] 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).^[19] Glutamate does not easily pass the blood brain barrier, but, instead, is transported by a high-affinity transport system.^[20] It can also be converted into glutamine.

See also

• Disodium glutamate
• Kainic acid
• Monosodium glutamate

References

External links

Look up glutamic acid in Wiktionary, the free dictionary.

• Glutamic acid MS Spectrum

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 

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 (≈10.8) Arginine (≈12.5) Histidine (≈6.1) Negative charge (pKa) Aspartic acid (≈3.9) Glutamic acid (≈4.1) Cysteine (≈8.3) Tyrosine (≈10.1) Other classifications Essential amino acid Ketogenic amino acid Glucogenic amino acid Non-proteinogenic amino acid