Glutamic acid
63541
225649570
2008-07-14T18:57:45Z
152.16.225.228
/* Neurotransmitter */
{{NatOrganicBox
| image=
<br>[[Image:Glutaminsäure - Glutamic acid.svg|240px|Chemical structure of Glutamic acid]] [[Image:L-glutamic-acid-3D-sticks2.png|200px|Chemical structure of the amino acid glutamate]]
| name=(2S)-2-aminopentanedioic acid
| PubChem = 611
| CAS = 56-86-0
| SMILES = N[C@@H](CCC(O)=O)C(O)=O
| C=5 | H=9 | N=1 | O=4
| mass=147.13 g/mol
}}
'''Glutamic acid''' (abbreviated as '''Glu''' or '''E'''; the abbreviation '''Glx''' or '''Z''' represents either glutamic acid or [[glutamine]]). The [[carboxylate anion]] of glutamic acid is known as '''glutamate''', and this is one of the 20 [[proteinogenic]] [[amino acid]]s. It is not among the human [[essential amino acid]]s. Its [[codons]] are GAA and GAG.
As its name indicates, glutamic acid has a [[carboxylic acid]] component to its [[side chain]]. At pH7, the [[amino group]] is [[protonate]]d and one or both of the [[carboxylic group]]s will be [[deprotonation|ionized]]. Hence, the species has a charge of −1, and is referred to as glutamate. The [[acid dissociation constant|pK<sub>a</sub>]] value for glutamic acid is 4.1, which means that below this pH, the carboxylic acid groups are not ionized in more than half of the molecules.
== History==
This compound was discovered in 1908 by the professor Kikunae Ikeda who worked in the Imperial University of Tokyo. He loved seaweed ( Kombu alga, in Japan) which is used like spice in traditional Japanese food. He tried to find the root of this flavour. He discovered that the origin of this taste was the glutamic acid. He isolated crystals of glutamic acid using a Kombu soup (one hundred grams of Kombu has nearly one gram of glutamic acid).
Moreover, he discovered that glutamate gave unique flavour to other foods. He called it "umami" (meaning "yumminess" in Japanese). This distinctive flavor has brought glutamate the title of "the elusive fifth taste" to join the more traditional flavors, sweet, salty, sour, and bitter. [http://nytimes.com/2008/03/05/dining/05glute.html?pagewanted=2&sq=umami&st=nyt&scp=4]
==Biosynthesis==
{| align="center" cellspacing="0" cellpadding="3" style="background: #FFFFFF; border: 1px solid #C0C090;"
! style="background-color: #F8EABA;" | Reactants
! style="background-color: #F8EABA;" | Products
! style="background-color: #F8EABA;" | Enzymes
|-
| [[Glutamine]] + H<sub>2</sub>O || → '''Glu''' + NH<sub>3</sub>
| [[Protein:GLS|GLS]], [[Protein:GLS2|GLS2]]
|-
| [[N acetylglutamic acid|NAcGlu]] + H<sub>2</sub>O || → '''Glu''' + Acetate
| (unknown)
|-
| [[Ketoglutaric acid|α-ketoglutarate]] + [[NADP]]H + NH<sub>4</sub><sup>+</sup> || → '''Glu''' + NADP<sup>+</sup> + H<sub>2</sub>O
| [[Protein:GLUD1|GLUD1]], [[Protein:GLUD2|GLUD2]]
|-
| [[Ketoglutaric acid|α-ketoglutarate]] + [[amino acid|α-amino acid]] || → '''Glu''' + α-oxo acid
| [[transaminase]]
|-
| [[1-pyrroline-5-carboxylate]] + [[Nicotinamide adenine dinucleotide|NAD<sup>+</sup>]] + H<sub>2</sub>O || → '''Glu''' + NADH
| [[Protein:ALDH4A1|ALDH4A1]]
|-
| [[N-formimino-L-glutamate]] + [[Folic acid|FH<sub>4</sub>]] || → '''Glu''' + [[Folic acid|5-formimino-FH<sub>4</sub>]]
| [[Protein:FTCD|FTCD]]
|-
|}
== Function and uses ==
=== Metabolism ===
Glutamate is a key molecule in cellular [[metabolism]]. In humans, dietary [[proteins]] are broken down by digestion into [[amino acids]], which serves 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:
: R<sub>1</sub>-amino acid + R<sub>2</sub>-α-ketoacid {{unicode|⇌}} R<sub>1</sub>-α-ketoacid + R<sub>2</sub>-amino acid
A very common α-ketoacid 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 {{unicode|⇌}} [[pyruvate]] + glutamate
: [[Aspartate]] + α-ketoglutarate {{unicode|⇌}} [[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 also 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]], as follows:
: glutamate + water + [[Nicotinamide adenine dinucleotide phosphate|NADP]]<sup>+</sup> → α-ketoglutarate + [[Nicotinamide adenine dinucleotide phosphate|NADPH]] + [[ammonia]] + H<sup>+</sup>
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.
=== Neurotransmitter ===
Glutamate is the most abundant excitatory [[neurotransmitter]] in the mammalian [[nervous system]]. At [[synapses|chemical synapses]], glutamate is stored in vesicles. [[Nerve impulses]] trigger release of glutamate from the pre-synaptic cell. In the opposing post-synaptic cell, [[glutamate receptors]], such as the [[NMDA receptor]], bind glutamate and are activated. Because of its role in [[synaptic plasticity]], it is believed that glutamic acid is involved in cognitive functions like [[learning]] and [[memory]] in the brain.
[[Glutamate transporter]]s{{ref_N|3|a}} are found in [[neuron]]al and [[glia]]l membranes. They rapidly remove glutamate from the [[extracellular]] space. In brain injury or disease, they can work in reverse and excess glutamate can accumulate outside cells. This process causes calcium ions to enter cells via [[NMDA receptor]] channels, leading to neuronal damage and eventual cell death, and is called [[excitotoxicity]]. The mechanisms of [[apoptosis|cell death]] include
* Damage to [[mitochondria]] from excessively high intracellular [[Calcium|Ca<sup>2+</sup>]];{{ref_N|4|a}}
* Glu/Ca<sup>2+</sup>-mediated promotion of [[transcription factor]]s for pro-apoptotic genes, or downregulation of transcription factors for anti-apoptotic genes.
Excitotoxicity due to glutamate occurs as part of the [[ischemic cascade]] and is associated with [[stroke]] and diseases like [[amyotrophic lateral sclerosis]], [[lathyrism]], autism, some forms of mental retardation and [[Alzheimer's disease]].
Glutamic acid has been implicated in epileptic [[seizure]]s. Microinjection of glutamic acid into neurons produces spontaneous [[depolarisation]]s around one [[second]] apart, and this firing pattern is similar to what is known as [[paroxysmal depolarizing shift]] in epileptic attacks. This change in the resting membrane potential at seizure foci could cause spontaneous opening of [[VOCC|voltage-activated calcium channel]]s, leading to glutamic acid release and further depolarization.
Experimental techniques to detect glutamate in intact cells include using a genetically-engineered [[nanosensor]]{{ref_N|2|a}}. The sensor is a fusion of a glutamate-binding protein and two fluorescent proteins. When glutamate binds, the fluorescence of the sensor under [[ultraviolet]] light changes by [[fluorescence resonance energy transfer|resonance between the two fluorophores]]. Introduction of the nanosensor into cells enables optical detection of the glutamate concentration. Synthetic analogs of glutamic acid that can be activated by [[ultraviolet]] light have also been described{{ref_N|6|}}. This method of rapidly uncaging by [[photostimulation]] is useful for mapping the connections between neurons, and understanding synapse function.
=== 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{{ref_N|7|}}. A gene expressed in [[glial cell]]s actively transports glutamate into the [[extracellular space]]{{ref_N|7|}}, while in the [[nucleus accumbens]] stimulating group II metabotropic glutamate receptors, this gene was found to reduce extracellular glutamate levels{{ref_N|8|}}. This raises the possibility that this extracellular glutamate plays an "endocrine-like" role as part of a larger homeostatic system.
==== GABA precursor ====
Glutamic acid also serves as the precursor for the synthesis of the inhibitory [[GABA]] in GABA-ergic neurons. This reaction is catalyzed by [[glutamic acid 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 is also abundant for the enzyme GAD, a direct immunological destruction occurs in the pancreas and the patients will have diabetes mellitus.
=== Flavor enhancer ===
{{main|glutamic acid (flavor)}}
Free glutamic acid is present in a wide variety of foods, including [[soy sauce]] and is responsible for one of the five [[basic taste]]s of the human sense of [[taste]] ([[umami]]). Glutamic acid is often used as a [[food additive]] and [[flavour enhancer]] in the form of its [[sodium]] [[salt]], [[monosodium glutamate]] (MSG).
=== Nutrient ===
All meats, poultry, fish, eggs, as well as dairy products are excellent sources of glutamic acid. Some protein-rich plant foods also serve as sources.[http://www.anyvitamins.com/glutamic-acid-info.htm]
Ninety-five percent of the dietary glutamate is metabolized by intestinal cells in a first pass {{ref_N|5|a}}
=== Plant growth ===
[[Auxigro]] is a plant growth preparation that contains 30% glutamic acid.
== Production ==
China-based Fufeng Group Limited is the largest producer of glutamic acid in the world, with capacity increasing to 300,000 tons at the end of 2006 from 180,000 tons during 2006, putting them at 25 - 30% of the Chinese market. Meihua is the second largest Chinese producer. Together, the top five producers have roughly 50% share in China. Chinese demand is roughly 1.1 million tons per year, while global demand, including China, is 1.7 million tons per year.
== Pharmacology ==
The drug [[phencyclidine]] (more commonly known as PCP) [[Receptor antagonist|antagonizes]] glutamic acid non-competitively at the NMDA receptor. For the same reasons, sub-anaesthetic doses of [[Ketamine]] have strong dissociative and hallucinogenic effects. Glutamate does not easily pass the [[blood brain barrier]], but instead this transport is mediated by a high affinity transport system <ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10736373 Transport of glutamate and other amino acids at the blood-brain barrier.Smith QR]</ref>. It can also be converted into [[glutamine]].
==Role in Sickle-Cell Disease==
A point mutation (valine in place of glutamic acid at position 6) in the β-globin chain of hemoglobin forms HbS. This variant of hemoglobin can cause sickle-cell anemia, where the abnormal hemoglobin are prone to polymerization when deoxygenated, thus distorting the erythrocyte which are removed by the spleen or cause microvascular obstruction (ischemic crises). This trait and disease is common in areas with high prevalence of ''Plasmodium falciparum'' (one of three Plasmodium species that causes malaria).
==See also==
*[[Kainic acid]]
== References ==
{{reflist}}
=== Other ===
{{Refbegin}}
# Nelson DL and Cox MM. ''Lehninger Principles of Biochemistry'', 4th edition.
# {{note_N|2|a}} [[Image:Free text.png]] {{cite journal | author=Okumoto, S., ''et al.'' | title=Detection of glutamate release from neurons by genetically encoded surface-displayed FRET nanosensors | journal=Proceedings of the National Academy of Sciences U.S.A | volume=102 | issue=24 | year=2005 | pages=8740–8745 | pmid=15939876 | doi = 10.1073/pnas.0503274102}} {{PMID_free|15939876}}
# {{note_N|3|a}} Molecular pharmacology of glutamate transporters, EAATs and VGLUTs. ''Brain Res Brain Res Rev. 2004 Jul; 45(3):250-65. {{PMID|15210307}}''
# {{note_N|4|a}} Delayed increase of Ca2+ influx elicited by glutamate: role in neuronal death. ''Mol Pharmacol. 1989 Jul;36(1):106-12; {{PMID|2568579}}''
# {{note_N|5|a}} [[Image:Free text.png]] {{cite journal | author=Reeds, P.J., ''et al.'' | title=Intestinal glutamate metabolism | journal=Journal of Nutrition | volume=130 | issue=4s | year=2000 | pages=978S–982S | pmid=10736365}}. [http://jn.nutrition.org/cgi/content/full/130/4/978S Free text]
# {{note_N|6|}} [[Image:Free text.png]] {{cite journal | author=Corrie, J.E., ''et al.'' | title=Postsynaptic activation at the squid giant synapse by photolytic release of L-glutamate from a 'caged' L-glutamate | journal=Journal of Physiology | volume=465 | year=1993 | issue=Jun | pages=1–8 | pmid=7901400}} [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=7901400| Free text]
# {{note_N|7|}} {{cite journal | author=Augustin H, Grosjean Y, Chen K, Sheng Q, Featherstone DE | title=Nonvesicular release of glutamate by glial xCT transporters suppresses glutamate receptor clustering in vivo | journal=Journal of Neuroscience | volume=27 | issue=1 | year=2007 | pages=111–123 | pmid=17202478 | doi = 10.1523/JNEUROSCI.4770-06.2007}}
# {{note_N|8|}} {{cite journal | author=Zheng Xi, Baker DA, Shen H, Carson DS, Kalivas PW | title=Group II metabotropic glutamate receptors modulate extracellular glutamate in the nucleus accumbens | journal=Journal of Pharmacology and Experimental Therapeutics | volume=300 | issue=1 | year=2002 | pages=162–171 | pmid=11752112 | doi=10.1124/jpet.300.1.162}}
{{Refend}}
{{AminoAcids}}
{{Glutamate_receptor_ligands}}
[[Category:Amino acids]]
[[Category:Proteinogenic amino acids]]
[[Category:Glucogenic amino acids]]
[[Category:Acidic amino acids]]
[[Category:Dicarboxylic acids]]
[[Category:Neurotransmitters]]
[[Category:Flavour enhancers]]
[[Category:Umami enhancers]]
[[bn:গ্লুটামিক অ্যাসিড]]
[[ca:Àcid glutàmic]]
[[cs:Kyselina glutamová]]
[[da:Glutaminsyre]]
[[de:Glutaminsäure]]
[[es:Ácido glutámico]]
[[eo:Glutama acido]]
[[fr:Acide glutamique]]
[[ko:글루탐산]]
[[id:Asam glutamat]]
[[it:Acido glutammico]]
[[he:חומצה גלוטמית]]
[[lv:Glutamīnskābe]]
[[lb:Glutamat]]
[[lt:Glutamo rūgštis]]
[[hu:Glutaminsav]]
[[nl:Glutaminezuur]]
[[ja:グルタミン酸]]
[[pl:Kwas glutaminowy]]
[[pt:Ácido glutâmico]]
[[ru:Глутаминовая кислота]]
[[sk:Kyselina glutámová]]
[[fi:Glutamiinihappo]]
[[sv:Glutaminsyra]]
[[th:กลูตาเมต]]
[[tr:Glutamik asit]]
[[uk:Глутамінова кислота]]
[[zh:穀氨酸]]