Product Code Database
Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of . 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 . Glutamic acid exists in two optically isomeric forms; the optical rotation -form is usually obtained by hydrolysis of gluten or from the waste waters of beet-sugar manufacture or by fermentation.Webster's Third New International Dictionary of the English Language Unabridged, Third Edition, 1971. Its molecular structure could be idealized as HOOC−CH()−()2−COOH, with two carboxylic acid groups −COOH and one amine −. However, in the solid state and mildly water solutions, the molecule assumes an electric charge zwitterion structure −OOC−CH()−()2−COOH. It is Genetic code by the GAA or GAG.
The acid can lose one proton from its second carboxyl group to form the conjugate base, the singly-negative anion glutamate −OOC−CH()−()2−COO−. This form of the compound is prevalent in acidity solutions. The glutamate neurotransmitter plays the principal role in neuron.Robert Sapolsky (2005), Biology and Human Behavior: The Neurological Origins of Individuality (2nd edition); The Teaching Company. pp. 19–20 of the Guide Book. This anion creates the savory umami flavor of foods and is found in glutamate flavorings such as monosodium glutamate (MSG). In Europe, it is classified as food additive E-numbers. In highly solutions the doubly negative anion −OOC−CH()−()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 aspartic acid, as glutamate is larger by one methylene group –CH2– group.
In sufficiently acidic environments, both carboxyl groups are protonated and the molecule becomes a cation with a single positive charge, HOOC−CH()−()2−COOH.
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()−()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 −OOC−CH()−()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 (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()−()2−COO−. The change in protonation state occurs at pH 9.47.William H. Brown and Lawrence S. Brown (2008), Organic Chemistry (5th edition). Cengage Learning. p. 1041. .
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:
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, as follows:
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.
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.
Glutamate toxicity can be reduced by Antioxidant, and the psychoactive principle of cannabis, tetrahydrocannabinol (THC), and the non psychoactive principle cannabidiol (CBD), and other Cannabinoid, is found to block glutamate neurotoxicity with a similar potency, and thereby potent antioxidants.
Optical isomerism
Glutamic acid is chiral; two mirror-image Enantiomer exist: (−), and (+). The form is more widely occurring in nature, but the form occurs in some special contexts, such as the bacterial capsule and of the bacteria (which produce it from the form with the enzyme glutamate racemase) and the liver of mammals.National Center for Biotechnology Information, " D-glutamate". PubChem Compound Database, CID=23327. Accessed 2017-02-17.
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. 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 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.
Synthesis
Biosynthesis
Glu + ammonia , Glu + acetate N-acetyl-glutamate synthase Glu + NADP+ + H2O , Glu + keto acid transaminase Glu + NADH Glu + folic acid 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. 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 hydrochloride salt.
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-Keto acid, typically catalysed by a transaminase. The reaction can be generalised as such:
Neurotransmitter
Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system. At synapses, glutamate is stored in Synaptic vesicle. Nerve impulses trigger the 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 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 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.
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). GABA-ergic neurons are identified (for research purposes) by revealing its activity (with the and immunohistochemistry methods) which is most abundant in the cerebellum and pancreas. (2025). 9780444527639 ISBN 9780444527639
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 and soy sauce, and glutamic acid is responsible for umami, one of the five 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.
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.C. M. Thiele, Concepts Magn. Reson. A, 2007, 30A, 65–80
Glutamate and aging
Brain glutamate levels tend to decline with age, and may be a useful as a marker of age-related diseases of the brain.
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 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. Eglumetad has also been demonstrated to act on the metabotropic glutamate receptor 3 (GRM3) of human adrenal cortex, downregulating aldosterone synthase, CYP11B1, and the production of adrenal (i.e. aldosterone and cortisol). 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.
See also
Further reading
External links
Categories: Amino Acids, Proteinogenic Amino Acids, Glucogenic Amino Acids, Excitatory Amino Acids, Flavor Enhancers, Umami Enhancers, Glutamates, Glutamic Acids, Excitatory Amino Acid Receptor Agonists, Glycine Receptor Agonists, Peripherally Selective Drugs, Chelating Agents, Glutamate, E-number Additives
|
|
