Glutamic acid

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Glutamic acid
L-Glutaminsaure - L-Glutamic acid.svg
Skeletal formula of L-glutamic acid
Glutamic-acid-from-xtal-view-2-3D-bs-17.png
Glutamic-acid-from-xtal-view-2-3D-sf.png
Sample of L-Glutamic acid.jpg
Names
IUPAC name
Glutamic acid
Systematic IUPAC name
2-Aminopentanedioic acid
Other names
  • 2-Aminoglutaric acid
Identifiers
  • l isomer: 56-86-0  Yes check.svgY
  • racemate: 617-65-2  Yes check.svgY
  • d isomer: 6893-26-1  Yes check.svgY
3D model (JSmol)
3DMet
1723801 (L) 1723799 (rac) 1723800 (D)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.009.567 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • l isomer:200-293-7
E number E620 (flavour enhancer)
3502 (L) 101971 (rac) 201189 (D)
KEGG
PubChem CID
UNII
  • InChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10) Yes check.svgY
    Key: WHUUTDBJXJRKMK-UHFFFAOYSA-N Yes check.svgY
  • 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
  • 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
AppearanceWhite crystalline powder
Density 1.4601 (20 °C)
Melting point 199 °C (390 °F; 472 K) decomposes
8.57 g/L [1]
Solubility Ethanol: 350 μg/100g (25 °C) [2]
Acidity (pKa)2.10, 4.07, 9.47 [3]
−78.5·10−6 cm3/mol
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
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.svgHealth 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 (symbol Glu or E; [4] the anionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a 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 C
5
H
9
NO
4
. Glutamic acid exists in two optically isomeric forms; the dextrorotatory L-form is usually obtained by hydrolysis of gluten or from the waste waters of beet-sugar manufacture or by fermentation. [5] [ full citation needed ] Its molecular structure could be idealized as HOOC−CH(NH
2
)−(CH
2
)2−COOH, with two carboxyl groups −COOH and one amino groupNH
2
. However, in the solid state and mildly acidic water solutions, the molecule assumes an electrically neutral zwitterion structure OOC−CH(NH+
3
)−(CH
2
)2−COOH. It is encoded by the codons GAA or GAG.

The acid can lose one proton from its second carboxyl group to form the conjugate base, the singly-negative anion glutamateOOC−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. [6] This anion creates the savory umami flavor of foods and is found in glutamate flavorings such as MSG. In Europe, it is classified as food additive 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. Glutamic Acid at physiological pH V2.svg
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. [11] 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. [11]

Optical isomerism

Glutamic acid is chiral; two mirror-image enantiomers exist: d(−), and l(+). The l form is more widely occurring in nature, but the d form occurs in some special contexts, such as the bacterial capsule and cell walls of the bacteria (which produce it from the l form with the enzyme glutamate racemase) and the liver of mammals. [12] [13]

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 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. [14] 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. [15] [16]

Synthesis

Biosynthesis

Reactants Products Enzymes
Glutamine + H2O Glu + NH3 GLS, GLS2
NAcGlu + H2O Glu + acetate N-Acetyl-glutamate synthase
α-Ketoglutarate + NADPH + NH4+Glu + NADP + + H2O GLUD1, GLUD2 [17]
α-Ketoglutarate + α-amino acid Glu + α-keto acid Transaminase
1-Pyrroline-5-carboxylate + NAD+ + H2OGlu + NADH ALDH4A1
N-Formimino-L-glutamate + 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 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, [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 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. [21] [22]

Neurotransmitter

Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system. [23] At chemical synapses, glutamate is stored in vesicles. Nerve impulses trigger the release of glutamate from the presynaptic cell. Glutamate acts on ionotropic and metabotropic (G-protein coupled) receptors. [23] 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. [24] 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. [25] 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. [26] A gene expressed 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]

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. [31]

Flavor enhancer

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 cheeses and soy sauce, and glutamic acid is responsible for umami, one of the five basic tastes 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, 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]

Role of glutamate in aging

Pharmacology

The drug phencyclidine (more commonly known as PCP or 'Angel Dust') 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 eglumetad (also known as eglumegad or LY354740), 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 eglumetad in those animals led to markedly reduced baseline cortisol levels (approximately 50 percent) in comparison to untreated control subjects. [34] Eglumetad 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). [35] Glutamate does not easily pass the blood brain barrier, but, instead, is transported by a high-affinity transport system. [36] [37] 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. [38] [39]

See also

Related Research Articles

α-Ketoglutaric acid Chemical compound

α-Ketoglutaric acid is a dicarboxylic acid, i.e., a short-chain fatty acid containing two carboxyl groups with C, O, and H standing for carbon, oxygen, and hydrogen, respectively. However, almost all animal tissues and extracellular fluids have a pH above 7. At these basic pH levels α-ketoglutaric acid exists almost exclusively as its conjugate base. That is, it has two negative electric charges due to its release of positively charged hydrogen from both of its now negatively charged carboxy groups, CO−2. This double negatively charge molecule is referred to as α-ketoglutarate or 2-oxoglutarate.

<span class="mw-page-title-main">GABA</span> Main inhibitory neurotransmitter in the mammalian brain

GABA is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.

<span class="mw-page-title-main">Aspartate transaminase</span> Enzyme involved in amino acid metabolism

Aspartate transaminase (AST) or aspartate aminotransferase, also known as AspAT/ASAT/AAT or (serum) glutamic oxaloacetic transaminase, is a pyridoxal phosphate (PLP)-dependent transaminase enzyme that was first described by Arthur Karmen and colleagues in 1954. AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in amino acid metabolism. AST is found in the liver, heart, skeletal muscle, kidneys, brain, red blood cells and gall bladder. Serum AST level, serum ALT level, and their ratio are commonly measured clinically as biomarkers for liver health. The tests are part of blood panels.

<span class="mw-page-title-main">Glutamate dehydrogenase</span> Hexameric enzyme

Glutamate dehydrogenase is an enzyme observed in both prokaryotes and eukaryotic mitochondria. The aforementioned reaction also yields ammonia, which in eukaryotes is canonically processed as a substrate in the urea cycle. Typically, the α-ketoglutarate to glutamate reaction does not occur in mammals, as glutamate dehydrogenase equilibrium favours the production of ammonia and α-ketoglutarate. Glutamate dehydrogenase also has a very low affinity for ammonia, and therefore toxic levels of ammonia would have to be present in the body for the reverse reaction to proceed. However, in brain, the NAD+/NADH ratio in brain mitochondria encourages oxidative deamination. In bacteria, the ammonia is assimilated to amino acids via glutamate and aminotransferases. In plants, the enzyme can work in either direction depending on environment and stress. Transgenic plants expressing microbial GLDHs are improved in tolerance to herbicide, water deficit, and pathogen infections. They are more nutritionally valuable.

<span class="mw-page-title-main">Ligand-gated ion channel</span> Type of ion channel transmembrane protein

Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter.

Molecular neuroscience is a branch of neuroscience that observes concepts in molecular biology applied to the nervous systems of animals. The scope of this subject covers topics such as molecular neuroanatomy, mechanisms of molecular signaling in the nervous system, the effects of genetics and epigenetics on neuronal development, and the molecular basis for neuroplasticity and neurodegenerative diseases. As with molecular biology, molecular neuroscience is a relatively new field that is considerably dynamic.

GABAB receptors (GABABR) are G-protein coupled receptors for gamma-aminobutyric acid (GABA), therefore making them metabotropic receptors, that are linked via G-proteins to potassium channels. The changing potassium concentrations hyperpolarize the cell at the end of an action potential. The reversal potential of the GABAB-mediated IPSP is −100 mV, which is much more hyperpolarized than the GABAA IPSP. GABAB receptors are found in the central nervous system and the autonomic division of the peripheral nervous system.

<span class="mw-page-title-main">Kainic acid</span> Chemical compound

Kainic acid, or kainate, is an acid that naturally occurs in some seaweed. Kainic acid is a potent neuroexcitatory amino acid agonist that acts by activating receptors for glutamate, the principal excitatory neurotransmitter in the central nervous system. Glutamate is produced by the cell's metabolic processes and there are four major classifications of glutamate receptors: NMDA receptors, AMPA receptors, kainate receptors, and the metabotropic glutamate receptors. Kainic acid is an agonist for kainate receptors, a type of ionotropic glutamate receptor. Kainate receptors likely control a sodium channel that produces excitatory postsynaptic potentials (EPSPs) when glutamate binds.

<span class="mw-page-title-main">Glutamate receptor</span> Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells

Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter, and also the precursor for GABA, the brain's main inhibitory neurotransmitter. Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation.

Neurotransmitter transporters are a class of membrane transport proteins that span the cellular membranes of neurons. Their primary function is to carry neurotransmitters across these membranes and to direct their further transport to specific intracellular locations. There are more than twenty types of neurotransmitter transporters.

<span class="mw-page-title-main">Quisqualic acid</span> Chemical compound

Quisqualic acid is an agonist of the AMPA, kainate, and group I metabotropic glutamate receptors. It is one of the most potent AMPA receptor agonists known. It causes excitotoxicity and is used in neuroscience to selectively destroy neurons in the brain or spinal cord. Quisqualic acid occurs naturally in the seeds of Quisqualis species.

<i>N</i>-Acetylaspartylglutamic acid Peptide neurotransmitter

N-Acetylaspartylglutamic acid is a peptide neurotransmitter and the third-most-prevalent neurotransmitter in the mammalian nervous system. NAAG consists of N-acetylaspartic acid (NAA) and glutamic acid coupled via a peptide bond.

<span class="mw-page-title-main">Branched-chain amino acid aminotransferase</span> Aminotransferase enzyme

Branched-chain amino acid aminotransferase (BCAT), also known as branched-chain amino acid transaminase, is an aminotransferase enzyme (EC 2.6.1.42) which acts upon branched-chain amino acids (BCAAs). It is encoded by the BCAT2 gene in humans. The BCAT enzyme catalyzes the conversion of BCAAs and α-ketoglutarate into branched chain α-keto acids and glutamate.

<span class="mw-page-title-main">4-aminobutyrate transaminase</span> Class of enzymes

In enzymology, 4-aminobutyrate transaminase, also called GABA transaminase or 4-aminobutyrate aminotransferase, or GABA-T, is an enzyme that catalyzes the chemical reaction:

In biochemistry, the glutamate–glutamine cycle is a cyclic metabolic pathway which maintains an adequate supply of the neurotransmitter glutamate in the central nervous system. Neurons are unable to synthesize either the excitatory neurotransmitter glutamate, or the inhibitory GABA from glucose. Discoveries of glutamate and glutamine pools within intercellular compartments led to suggestions of the glutamate–glutamine cycle working between neurons and astrocytes. The glutamate/GABA–glutamine cycle is a metabolic pathway that describes the release of either glutamate or GABA from neurons which is then taken up into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of either glutamate or GABA.

<span class="mw-page-title-main">Keto acid</span> Organic compounds with a –COOH group and a C=O group

In organic chemistry, keto acids or ketoacids are organic compounds that contain a carboxylic acid group and a ketone group. In several cases, the keto group is hydrated. The alpha-keto acids are especially important in biology as they are involved in the Krebs citric acid cycle and in glycolysis.

<span class="mw-page-title-main">Quisqualamine</span> Chemical compound

Quisqualamine is the α-decarboxylated analogue of quisqualic acid, as well as a relative of the neurotransmitters glutamate and γ-aminobutyric acid (GABA). α-Decarboxylation of excitatory amino acids can produce derivatives with inhibitory effects. Indeed, unlike quisqualic acid, quisqualamine has central depressant and neuroprotective properties and appears to act predominantly as an agonist of the GABAA receptor and also to a lesser extent as an agonist of the glycine receptor, due to the facts that its actions are inhibited in vitro by GABAA antagonists like bicuculline and picrotoxin and by the glycine antagonist strychnine, respectively. Mg2+ and DL-AP5, NMDA receptor blockers, CNQX, an antagonist of both the AMPA and kainate receptors, and 2-hydroxysaclofen, a GABAB receptor antagonist, do not affect quisqualamine's actions in vitro, suggesting that it does not directly affect the ionotropic glutamate receptors or the GABAB receptor in any way. Whether it binds to and acts upon any of the metabotropic glutamate receptors like its analogue quisqualic acid however is unclear.

Dicarboxylic aminoaciduria is a rare form of aminoaciduria which is an autosomal recessive disorder of urinary glutamate and aspartate due to genetic errors related to transport of these amino acids. Mutations resulting in a lack of expression of the SLC1A1 gene, a member of the solute carrier family, are found to cause development of dicarboxylic aminoaciduria in humans. SLC1A1 encodes for EAAT3 which is found in the neurons, intestine, kidney, lung, and heart. EAAT3 is part of a family of high affinity glutamate transporters which transport both glutamate and aspartate across the plasma membrane.

<span class="mw-page-title-main">Glutamate (neurotransmitter)</span> Anion of glutamic acid in its role as a neurotransmitter

In neuroscience, glutamate is the anion of glutamic acid in its role as a neurotransmitter. It is by a wide margin the most abundant excitatory neurotransmitter in the vertebrate nervous system. It is used by every major excitatory function in the vertebrate brain, accounting in total for well over 90% of the synaptic connections in the human brain. It also serves as the primary neurotransmitter for some localized brain regions, such as cerebellum granule cells.

Ionotropic GABA receptors (iGABARs) are ligand-gated ion channel of the GABA receptors class which are activated by gamma-aminobutyric acid (GABA), and include:

References

  1. "L-Glutamic acid". National Library of Medicine. Retrieved 24 June 2023.
  2. Belitz, H.-D.; Grosch, Werner; Schieberle, Peter (27 February 2009). Food Chemistry. Springer. 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. Saffran, M. (April 1998). "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?". Biochemical Education. 26 (2): 116–118. doi:10.1016/S0307-4412(97)00167-2.
  8. 1 2 Albert Neuberger (1936), "Dissociation constants and structures of glutamic acid and its esters". Biochemical Journal, volume 30, issue 11, article CCXCIII, pp. 2085–2094. PMC   1263308.
  9. 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. Bibcode:1989TcAc..141..297R. doi:10.1016/0040-6031(89)87065-0.
  10. 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. Bibcode:1972JCCry...2..225L. doi:10.1007/BF01246639. S2CID   93590487.
  11. 1 2 3 William H. Brown and Lawrence S. Brown (2008), Organic Chemistry (5th edition). Cengage Learning. p. 1041. ISBN   0495388572 , 978-0495388579.
  12. National Center for Biotechnology Information, "D-glutamate". PubChem Compound Database, CID=23327. Accessed 2017-02-17.
  13. Liu, L.; Yoshimura, T.; Endo, K.; Kishimoto, K.; Fuchikami, Y.; Manning, J. M.; 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.
  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. Alvise Perosa; Fulvio Zecchini (2007). Methods and Reagents for Green Chemistry: An Introduction. John Wiley & Sons. p. 25. ISBN   978-0-470-12407-9.
  18. Michael C. Flickinger (2010). Encyclopedia of Industrial Biotechnology: Bioprocess, Bioseparation, and Cell Technology, 7 Volume Set. Wiley. pp. 215–225. ISBN   978-0-471-79930-6.
  19. 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. PMID   22006024.
  20. 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 (BBA) - Reviews on Cancer. 1846 (1): 66–74. doi:10.1016/j.bbcan.2014.04.004. PMID   24747768.
  21. 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): 1669–1670. doi:10.1093/neuonc/nou152. PMC   4232089 . PMID   25074540.
  22. 1 2 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. doi: 10.1093/jn/130.4.1007s . PMID   10736372.
  23. 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. S2CID   37400348.
  24. 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. Bibcode:2010PNAS..107.6526O. doi: 10.1073/pnas.0913154107 . PMC   2851965 . PMID   20308566.
  25. 1 2 Augustin H, Grosjean Y, Chen K, Sheng Q, Featherstone DE (2007). "Nonvesicular Release of Glutamate by Glial xCT Transporters Suppresses Glutamate Receptor Clustering In Vivo". Journal of Neuroscience. 27 (1): 111–123. doi:10.1523/JNEUROSCI.4770-06.2007. PMC   2193629 . PMID   17202478.
  26. 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.
  27. Bak, Lasse K.; Schousboe, Arne; Waagepetersen, Helle S. (August 2006). "The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer". Journal of Neurochemistry. 98 (3): 641–653. doi:10.1111/j.1471-4159.2006.03913.x. ISSN   0022-3042. PMID   16787421.
  28. Kerr, D.I.B.; Ong, J. (January 1995). "GABAB receptors" . Pharmacology & Therapeutics. 67 (2): 187–246. doi:10.1016/0163-7258(95)00016-A. PMID   7494864.
  29. Krueger, Christian; Stöker, Winfried; Schlosser, Michael (2007). "GLUTAMIC ACID DECARBOXYLASE AUTOANTIBODIES" . Autoantibodies (2nd ed.). pp. 369–378. doi:10.1016/B978-044452763-9/50052-4. ISBN   978-0-444-52763-9.
  30. Newsome, Scott D.; Johnson, Tory (15 August 2022). "Stiff Person Syndrome Spectrum Disorders; More Than Meets the Eye". Journal of Neuroimmunology. 369: 577915. doi:10.1016/j.jneuroim.2022.577915. ISSN   0165-5728. PMC   9274902 . PMID   35717735.
  31. Reeds, P.J.; et al. (1 April 2000). "Intestinal glutamate metabolism". Journal of Nutrition. 130 (4s): 978S–982S. doi: 10.1093/jn/130.4.978S . PMID   10736365.
  32. C. M. Thiele, Concepts Magn. Reson. A, 2007, 30A, 65–80
  33. 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): 607–612, 617. doi:10.1017/S1092852900002157. PMID   15573025. S2CID   6029856.
  34. 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 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. S2CID   3357749.
  35. Smith, Quentin R. (April 2000). "Transport of glutamate and other amino acids at the blood–brain barrier". The Journal of Nutrition . 130 (4S Suppl): 1016S–1022S. doi: 10.1093/jn/130.4.1016S . PMID   10736373.
  36. Hawkins, Richard A. (September 2009). "The blood-brain barrier and glutamate". The American Journal of Clinical Nutrition . 90 (3): 867S–874S. doi:10.3945/ajcn.2009.27462BB. PMC   3136011 . 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.
  37. Hampson, Aidan J. (1998). "Cannabidiol and (−)Δ9-tetrahydrocannabinol are neuroprotective antioxidants". Proc Natl Acad Sci USA. 95 (14): 8268–8273. doi: 10.1073/pnas.95.14.8268 . PMC   20965 . PMID   9653176.
  38. Hampson, Aidan J. (2006). "Neuroprotective Antioxidants from Marijuana". Annals of the New York Academy of Sciences. 899 (1): 274–282. doi:10.1111/j.1749-6632.2000.tb06193.x. S2CID   39496546.

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