Glutamic Acid

<p><b >Glutamic acid</b> (abbreviated as <b >Glu</b> or <b >E</b>) is one of the 20-22 <a href="http://en.wikipedia.org/wiki/Proteinogenic_amino_acid" title="Proteinogenic amino acid" >proteinogenic amino acids</a>, and its <a href="http://en.wikipedia.org/wiki/Codons" title="Codons" class="mw-redirect" >codons</a> are GAA and GAG. It is a non-<a href="http://en.wikipedia.org/wiki/Essential_amino_acid" title="Essential amino acid" >essential amino acid</a>. The <a href="http://en.wikipedia.org/wiki/Carboxylate_anion" title="Carboxylate anion" class="mw-redirect" >carboxylate anions</a> and <a href="http://en.wikipedia.org/wiki/Salt_(chemistry)" title="Salt (chemistry)" >salts</a> of glutamic acid are known as <b >glutamates</b>. In <a href="http://en.wikipedia.org/wiki/Neuroscience" title="Neuroscience" >neuroscience</a>, glutamate is an important <a href="http://en.wikipedia.org/wiki/Neurotransmitter" title="Neurotransmitter" >neurotransmitter</a> that plays a key role in <a href="http://en.wikipedia.org/wiki/Long-term_potentiation" title="Long-term potentiation" >long-term potentiation</a> and is important for learning and memory.<sup id="cite_ref-twsNovK11_2-0" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-twsNovK11-2" >[3]</a></sup>

<h2 >Chemistry</h2>

<p >The <a href="http://en.wikipedia.org/wiki/Side_chain" title="Side chain" >side chain</a> <a href="http://en.wikipedia.org/wiki/Carboxylic_acid" title="Carboxylic acid" >carboxylic acid</a> <a href="http://en.wikipedia.org/wiki/Functional_group" title="Functional group" >functional group</a> has <a href="http://en.wikipedia.org/wiki/Acid_dissociation_constant" title="Acid dissociation constant" >pK<sub >a</sub></a> of 4.1 and exists in its <a href="http://en.wikipedia.org/wiki/Negatively_charged" title="Negatively charged" class="mw-redirect" >negatively charged</a> <a href="http://en.wikipedia.org/wiki/Deprotonation" title="Deprotonation" >deprotonated</a> <a href="http://en.wikipedia.org/wiki/Carboxylate" title="Carboxylate" >carboxylate</a> form at pHs greater than 4.1 therefore it is also negatively charged at <a href="http://en.wikipedia.org/wiki/Physiological_pH" title="Physiological pH" class="mw-redirect" >physiological pH</a> ranging from 7.35 to 7.45.

 </p>

<h2 >[<a href="http://en.wikipedia.org/w/index.php?title=Glutamic_acid&action=edit&section=2" title="Edit section: History" >edit</a>]History</h2>

<div class="rellink relarticle mainarticle" >Main article: <a href="http://en.wikipedia.org/wiki/Glutamic_acid_(flavor)" title="Glutamic acid (flavor)" >Glutamic acid (flavor)</a></div>

<p >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 Leopold Ritthausen who treated wheat <a href="http://en.wikipedia.org/wiki/Gluten" title="Gluten" >gluten</a> (for which it was named) with sulfuric acid.<sup id="cite_ref-3" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-3" >[4]</a></sup> In 1907 Japanese researcher <a href="http://en.wikipedia.org/wiki/Kikunae_Ikeda" title="Kikunae Ikeda" >Kikunae Ikeda</a> of the <a href="http://en.wikipedia.org/wiki/Tokyo_Imperial_University" title="Tokyo Imperial University" class="mw-redirect" >Tokyo Imperial University</a> identified brown crystals left behind after the evaporation of a large amount of<a href="http://en.wikipedia.org/wiki/Kombu" title="Kombu" >kombu</a> 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 <a href="http://en.wikipedia.org/wiki/Umami" title="Umami" >umami</a>. He then patented a method of mass-producing a crystalline salt of glutamic acid, <a href="http://en.wikipedia.org/wiki/Monosodium_glutamate" title="Monosodium glutamate" >monosodium glutamate</a>.<sup id="cite_ref-guardian_4-0" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-guardian-4" >[5]</a></sup><sup id="cite_ref-5" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-5" >[6]</a></sup></p>

<h2 >Biosynthesis</h2>

<tr>

<th ><a href="http://en.wikipedia.org/wiki/Reactants" title="Reactants" class="mw-redirect" >Reactants</a></th>

<th ><a href="http://en.wikipedia.org/wiki/Product_(chemistry)" title="Product (chemistry)" >Products</a></th>

<th ><a href="http://en.wikipedia.org/wiki/Enzymes" title="Enzymes" class="mw-redirect" >Enzymes</a></th>

</tr>

<tr>

<td><a href="http://en.wikipedia.org/wiki/Glutamine" title="Glutamine" >Glutamine</a> + <a href="http://en.wikipedia.org/wiki/Water" title="Water" >H<sub >2</sub>O</a></td>

</tr>

<tr>

<td><a href="http://en.wikipedia.org/wiki/N_acetylglutamic_acid" title="N acetylglutamic acid" class="mw-redirect" >NAcGlu</a> + <a href="http://en.wikipedia.org/wiki/Water" title="Water" >H<sub >2</sub>O</a></td>

<td>→ <b>Glu</b> + <a href="http://en.wikipedia.org/wiki/Acetate" title="Acetate" >Acetate</a></td>

<td>(unknown)</td>

</tr>

<tr>

<td><a href="http://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid" title="Alpha-Ketoglutaric acid" >α-ketoglutarate</a> + <a href="http://en.wikipedia.org/wiki/NADP" title="NADP" class="mw-redirect" >NADP</a>H + NH<sub >4</sub><sup >+</sup></td>

</tr>

<tr>

<td><a href="http://en.wikipedia.org/wiki/Alpha-Ketoglutaric_acid" title="Alpha-Ketoglutaric acid" >α-ketoglutarate</a> + <a href="http://en.wikipedia.org/wiki/Amino_acid" title="Amino acid" >α-amino acid</a></td>

<td><a href="http://en.wikipedia.org/wiki/Transaminase" title="Transaminase" >transaminase</a></td>

</tr>

<tr>

<td><a href="http://en.wikipedia.org/wiki/1-Pyrroline-5-carboxylate" title="1-Pyrroline-5-carboxylate" class="mw-redirect" >1-Pyrroline-5-carboxylate</a> + <a href="http://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide" title="Nicotinamide adenine dinucleotide" >NAD<sup >+</sup></a> + H<sub >2</sub>O</td>

</tr>

<tr>

<td><a href="http://en.wikipedia.org/wiki/N-formimino-L-glutamate" title="N-formimino-L-glutamate" class="mw-redirect" >N-formimino-L-glutamate</a> + <a href="http://en.wikipedia.org/wiki/Folic_acid" title="Folic acid" >FH<sub >4</sub></a></td>

<td>→ <b>Glu</b> + <a href="http://en.wikipedia.org/wiki/Folic_acid" title="Folic acid" >5-formimino-FH<sub >4</sub></a></td>

</tr>

</tbody></table>

 </p>

<h2 >[<a href="http://en.wikipedia.org/w/index.php?title=Glutamic_acid&action=edit&section=4" title="Edit section: Function and uses" >edit</a>]Function and uses</h2>

<h3 >Metabolism</h3>

<p >Glutamate is a key compound in cellular <a href="http://en.wikipedia.org/wiki/Metabolism" title="Metabolism" >metabolism</a>. In humans, dietary <a href="http://en.wikipedia.org/wiki/Proteins" title="Proteins" class="mw-redirect" >proteins</a> are broken down by digestion into <a href="http://en.wikipedia.org/wiki/Amino_acids" title="Amino acids" class="mw-redirect" >amino acids</a>, which serve as metabolic fuel for other functional roles in the body. A key process in amino acid degradation is <a href="http://en.wikipedia.org/wiki/Transamination" title="Transamination" >transamination</a>, in which the amino group of an amino acid is transferred to an α-ketoacid, typically catalysed by a<a href="http://en.wikipedia.org/wiki/Transaminase" title="Transaminase" >transaminase</a>. The reaction can be generalised as such:</p>

<dl >

<dd >R<sub >1</sub>-amino acid + R<sub >2</sub>-α-ketoacid ⇌ R<sub >1</sub>-α-ketoacid + R<sub >2</sub>-amino acid</dd>

</dl>

<p >A very common α-keto acid is α-ketoglutarate, an intermediate in the <a href="http://en.wikipedia.org/wiki/Citric_acid_cycle" title="Citric acid cycle" >citric acid cycle</a>. 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:</p>

<dl >

<dd ><a href="http://en.wikipedia.org/wiki/Alanine" title="Alanine" >Alanine</a> + α-ketoglutarate ⇌ <a href="http://en.wikipedia.org/wiki/Pyruvate" title="Pyruvate" class="mw-redirect" >pyruvate</a> + glutamate</dd>

</dl>

<dl >

<dd ><a href="http://en.wikipedia.org/wiki/Aspartate" title="Aspartate" class="mw-redirect" >Aspartate</a> + α-ketoglutarate ⇌ <a href="http://en.wikipedia.org/wiki/Oxaloacetate" title="Oxaloacetate" class="mw-redirect" >oxaloacetate</a> + glutamate</dd>

</dl>

<p >Both pyruvate and oxaloacetate are key components of cellular metabolism, contributing as substrates or intermediates in fundamental processes such as <a href="http://en.wikipedia.org/wiki/Glycolysis" title="Glycolysis" >glycolysis</a>,<a href="http://en.wikipedia.org/wiki/Gluconeogenesis" title="Gluconeogenesis" >gluconeogenesis</a>, and the <a href="http://en.wikipedia.org/wiki/Citric_acid_cycle" title="Citric acid cycle" >citric acid cycle</a>.

Glutamate also plays an important role in the body's disposal of excess or waste <a href="http://en.wikipedia.org/wiki/Nitrogen" title="Nitrogen" >nitrogen</a>. Glutamate undergoes <a href="http://en.wikipedia.org/wiki/Deamination" title="Deamination" >deamination</a>, an oxidative reaction catalysed by <a href="http://en.wikipedia.org/wiki/Glutamate_dehydrogenase" title="Glutamate dehydrogenase" >glutamate dehydrogenase</a>,<sup id="cite_ref-springerlink_6-1" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-springerlink-6" >[7]</a></sup> as follows:</p>

<dl >

<dd >glutamate + H<sub >2</sub>O + <a href="http://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide_phosphate" title="Nicotinamide adenine dinucleotide phosphate" >NADP</a><sup >+</sup> → α-ketoglutarate + <a href="http://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide_phosphate" title="Nicotinamide adenine dinucleotide phosphate" >NADPH</a> + NH<sub >3</sub> + H<sup >+</sup></dd>

</dl>

<p >Ammonia (as <a href="http://en.wikipedia.org/wiki/Ammonium" title="Ammonium" >ammonium</a>) is then excreted predominantly as <a href="http://en.wikipedia.org/wiki/Urea" title="Urea" >urea</a>, synthesised in the <a href="http://en.wikipedia.org/wiki/Liver" title="Liver" >liver</a>. 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.</p>

<h3 >Neurotransmitter</h3>

<p >Glutamate is the most abundant excitatory <a href="http://en.wikipedia.org/wiki/Neurotransmitter" title="Neurotransmitter" >neurotransmitter</a> in the vertebrate <a href="http://en.wikipedia.org/wiki/Nervous_system" title="Nervous system" >nervous system</a>.<sup id="cite_ref-pmid10736372_7-0" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-pmid10736372-7" >[8]</a></sup> At <a href="http://en.wikipedia.org/wiki/Synapses" title="Synapses" class="mw-redirect" >chemical synapses</a>, glutamate is stored in <a href="http://en.wikipedia.org/wiki/Synaptic_vesicle" title="Synaptic vesicle" >vesicles</a>. <a href="http://en.wikipedia.org/wiki/Nerve_impulses" title="Nerve impulses" class="mw-redirect" >Nerve impulses</a> trigger release of glutamate from the pre-synaptic cell. In the opposing post-synaptic cell, <a href="http://en.wikipedia.org/wiki/Glutamate_receptors" title="Glutamate receptors" class="mw-redirect" >glutamate receptors</a>, such as the <a href="http://en.wikipedia.org/wiki/NMDA_receptor" title="NMDA receptor" >NMDA receptor</a>, bind glutamate and are activated. Because of its role in <a href="http://en.wikipedia.org/wiki/Synaptic_plasticity" title="Synaptic plasticity" >synaptic plasticity</a>, glutamate is involved in cognitive functions like <a href="http://en.wikipedia.org/wiki/Learning" title="Learning" >learning</a> and <a href="http://en.wikipedia.org/wiki/Memory" title="Memory" >memory</a> in the brain.<sup id="cite_ref-8" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-8" >[9]</a></sup> The form of plasticity known as <a href="http://en.wikipedia.org/wiki/Long-term_potentiation" title="Long-term potentiation" >long-term potentiation</a> takes place at glutamatergic synapses in the <a href="http://en.wikipedia.org/wiki/Hippocampus" title="Hippocampus" >hippocampus</a>, <a href="http://en.wikipedia.org/wiki/Neocortex" title="Neocortex" >neocortex</a>, 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/<a href="http://en.wikipedia.org/wiki/Volume_transmission" title="Volume transmission" class="mw-redirect" >volume transmission</a>.<sup id="cite_ref-9" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-9" >[10]</a></sup></p>

<p>

<a href="http://en.wikipedia.org/wiki/Glutamate_transporter" title="Glutamate transporter" class="mw-redirect" >Glutamate transporters</a><sup id="cite_ref-10" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-10" >[11]</a></sup> are found in <a href="http://en.wikipedia.org/wiki/Neuron" title="Neuron" >neuronal</a> and <a href="http://en.wikipedia.org/wiki/Glia" title="Glia" class="mw-redirect" >glial</a> membranes. They rapidly remove glutamate from the <a href="http://en.wikipedia.org/wiki/Extracellular" title="Extracellular" >extracellular</a> 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 <a href="http://en.wikipedia.org/wiki/NMDA_receptor" title="NMDA receptor" >NMDA receptor</a> channels, leading to neuronal damage and eventual cell death, and is called <a href="http://en.wikipedia.org/wiki/Excitotoxicity" title="Excitotoxicity" >excitotoxicity</a>. The mechanisms of <a href="http://en.wikipedia.org/wiki/Apoptosis" title="Apoptosis" >cell death</a> include</p>

<ul >

<li >Damage to <a href="http://en.wikipedia.org/wiki/Mitochondria" title="Mitochondria" class="mw-redirect" >mitochondria</a> from excessively high intracellular <a href="http://en.wikipedia.org/wiki/Calcium" title="Calcium" >Ca<sup >2+</sup></a><sup id="cite_ref-11" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-11" >[12]</a></sup></li>

</ul>

<ul >

<li >Glu/Ca<sup >2+</sup>-mediated promotion of <a href="http://en.wikipedia.org/wiki/Transcription_factor" title="Transcription factor" >transcription factors</a> for pro-apoptotic genes, or downregulation of transcription factors for anti-apoptotic genes</li>

</ul>

<p ><a href="http://en.wikipedia.org/wiki/Excitotoxicity" title="Excitotoxicity" >Excitotoxicity</a> due to glutamate occurs as part of the <a href="http://en.wikipedia.org/wiki/Ischemic_cascade" title="Ischemic cascade" >ischemic cascade</a> and is associated with <a href="http://en.wikipedia.org/wiki/Stroke" title="Stroke" >stroke</a><sup id="cite_ref-twsNovK11_2-1" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-twsNovK11-2" >[3]</a></sup> and diseases like <a href="http://en.wikipedia.org/wiki/Amyotrophic_lateral_sclerosis" title="Amyotrophic lateral sclerosis" >amyotrophic lateral sclerosis</a>, <a href="http://en.wikipedia.org/wiki/Lathyrism" title="Lathyrism" >lathyrism</a>, <a href="http://en.wikipedia.org/wiki/Autism" title="Autism" >autism</a>, some forms of <a href="http://en.wikipedia.org/wiki/Mental_retardation" title="Mental retardation" >mental retardation</a>, and <a href="http://en.wikipedia.org/wiki/Alzheimer%27s_disease" title="Alzheimer's disease" >Alzheimer's disease</a>.<sup id="cite_ref-twsNovK11_2-2" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-twsNovK11-2" >[3]</a></sup><sup id="cite_ref-12" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-12" >[13]</a></sup>

Glutamic acid has been implicated in epileptic <a href="http://en.wikipedia.org/wiki/Seizure" title="Seizure" class="mw-redirect" >seizures</a>. Microinjection of glutamic acid into neurons produces spontaneous <a href="http://en.wikipedia.org/wiki/Depolarisation" title="Depolarisation" class="mw-redirect" >depolarisations</a> around one <a href="http://en.wikipedia.org/wiki/Second" title="Second" >second</a> apart, and this firing pattern is similar to what is known as <a href="http://en.wikipedia.org/wiki/Paroxysmal_depolarizing_shift" title="Paroxysmal depolarizing shift" >paroxysmal depolarizing shift</a> in epileptic attacks. This change in the resting membrane potential at seizure foci could cause spontaneous opening of <a href="http://en.wikipedia.org/wiki/VOCC" title="VOCC" class="mw-redirect" >voltage-activated calcium channels</a>, leading to glutamic acid release and further depolarization.

Experimental techniques to detect glutamate in intact cells include using a genetically-engineered <a href="http://en.wikipedia.org/wiki/Nanosensor" title="Nanosensor" >nanosensor</a>.<sup id="cite_ref-13" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-13" >[14]</a></sup> The sensor is a fusion of a glutamate-binding protein and two fluorescent proteins. When glutamate binds, the fluorescence of the sensor under <a href="http://en.wikipedia.org/wiki/Ultraviolet" title="Ultraviolet" >ultraviolet</a> light changes by <a href="http://en.wikipedia.org/wiki/Fluorescence_resonance_energy_transfer" title="Fluorescence resonance energy transfer" class="mw-redirect" >resonance between the two fluorophores</a>. Introduction of the nanosensor into cells enables optical detection of the glutamate concentration. Synthetic analogs of glutamic acid that can be activated by <a href="http://en.wikipedia.org/wiki/Ultraviolet" title="Ultraviolet" >ultraviolet</a> light and <a href="http://en.wikipedia.org/wiki/Two-photon_excitation_microscopy" title="Two-photon excitation microscopy" >two-photon excitation microscopy</a> have also been described.<sup id="cite_ref-14" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-14" >[15]</a></sup> This method of rapidly uncaging by <a href="http://en.wikipedia.org/wiki/Photostimulation" title="Photostimulation" >photostimulation</a> is useful for mapping the connections between neurons, and understanding synapse function.

Evolution of glutamate receptors is entirely the opposite in invertebrates, in particular, arthropods and nematodes, where glutamate stimulates glutamate-gated chloride channels.<sup class="Template-Fact" >[<i><a href="http://en.wikipedia.org/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed" >citation needed</a></i>]</sup> The beta subunits of the receptor respond with very high affinity to glutamate and glycine.<sup id="cite_ref-15" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-15" >[16]</a></sup> Targeting these receptors has been the therapeutic goal of<a href="http://en.wikipedia.org/wiki/Anthelmintic" title="Anthelmintic" >anthelmintic</a> therapy using <a href="http://en.wikipedia.org/wiki/Avermectin" title="Avermectin" >avermectins</a>. Avermectins target the alpha-subunit of glutamate-gated chloride channels with high affinity.<sup id="cite_ref-16" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-16" >[17]</a></sup> These receptors have also been described in arthropods, such as <i>Drosophila melanogaster</i><sup id="cite_ref-17" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-17" >[18]</a></sup> and <i>Lepeophtheirus salmonis</i>.<sup id="cite_ref-18" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-18" >[19]</a></sup> Irreversible activation of these receptors with avermectins results in hyperpolarization at synapses and neuromuscular junctions resulting in flaccid paralysis and death of nematodes and arthropods.</p>

L-Glutamate at physiological conditions</div>

</div>

<h3 >Brain nonsynaptic glutamatergic signaling circuits</h3>

<p >Extracellular glutamate in <i><a href="http://en.wikipedia.org/wiki/Drosophila" title="Drosophila" >Drosophila</a></i> brains has been found to regulate postsynaptic glutamate receptor clustering, via a process involving receptor desensitization.<sup id="cite_ref-augustin_19-0" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-augustin-19" >[20]</a></sup> A gene expressed in <a href="http://en.wikipedia.org/wiki/Glial_cell" title="Glial cell" class="mw-redirect" >glial cells</a> actively transports glutamate into the <a href="http://en.wikipedia.org/wiki/Extracellular_space" title="Extracellular space" class="mw-redirect" >extracellular space</a>,<sup id="cite_ref-augustin_19-1" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-augustin-19" >[20]</a></sup>while, in the <a href="http://en.wikipedia.org/wiki/Nucleus_accumbens" title="Nucleus accumbens" >nucleus accumbens</a>-stimulating group II metabotropic glutamate receptors, this gene was found to reduce extracellular glutamate levels.<sup id="cite_ref-20" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-20" >[21]</a></sup> This raises the possibility that this extracellular glutamate plays an "endocrine-like" role as part of a larger homeostatic system.</p>

<h4 >[<a href="http://en.wikipedia.org/w/index.php?title=Glutamic_acid&action=edit&section=8" title="Edit section: GABA precursor" >edit</a>]GABA precursor</h4>

<p >Glutamate also serves as the precursor for the synthesis of the inhibitory <a href="http://en.wikipedia.org/wiki/GABA" title="GABA" class="mw-redirect" >GABA</a> in GABA-ergic neurons. This reaction is catalyzed by <a href="http://en.wikipedia.org/wiki/Glutamate_decarboxylase" title="Glutamate decarboxylase" >glutamate decarboxylase</a> (GAD), which is most abundant in the <a href="http://en.wikipedia.org/wiki/Cerebellum" title="Cerebellum" >cerebellum</a> and <a href="http://en.wikipedia.org/wiki/Pancreas" title="Pancreas" >pancreas</a>.

<a href="http://en.wikipedia.org/wiki/Stiff-man_syndrome" title="Stiff-man syndrome" class="mw-redirect" >Stiff-man syndrome</a> 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.</p>

<h3 >Flavor enhancer</h3>

<div class="rellink relarticle mainarticle" >Main article: <a href="http://en.wikipedia.org/wiki/Glutamic_acid_(flavor)" title="Glutamic acid (flavor)" >Glutamic acid (flavor)</a></div>

<p >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 <a href="http://en.wikipedia.org/wiki/Cheese" title="Cheese" >cheese</a> and <a href="http://en.wikipedia.org/wiki/Soy_sauce" title="Soy sauce" >soy sauce</a>, and is responsible for <a href="http://en.wikipedia.org/wiki/Umami" title="Umami" >umami</a>, one of the five <a href="http://en.wikipedia.org/wiki/Basic_taste" title="Basic taste" class="mw-redirect" >basic tastes</a> of the human sense of <a href="http://en.wikipedia.org/wiki/Taste" title="Taste" >taste</a>. Glutamic acid is often used as a <a href="http://en.wikipedia.org/wiki/Food_additive" title="Food additive" >food additive</a> and <a href="http://en.wikipedia.org/wiki/Flavour_enhancer" title="Flavour enhancer" >flavour enhancer</a> in the form of its <a href="http://en.wikipedia.org/wiki/Sodium" title="Sodium" >sodium</a> <a href="http://en.wikipedia.org/wiki/Salt" title="Salt" >salt</a> <a href="http://en.wikipedia.org/wiki/Monosodium_glutamate" title="Monosodium glutamate" >monosodium glutamate</a> (MSG).</p>

<h3 >Nutrient</h3>

<p >All meats, poultry, fish, eggs, dairy products, and <a href="http://en.wikipedia.org/wiki/Kombu" title="Kombu" >kombu</a> are excellent sources of glutamic acid. Some protein-rich plant foods also serve as sources. Thirty 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.<sup id="cite_ref-21" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-21" >[22]</a></sup></p>

<h3 >Plant growth</h3>

<p ><a href="http://en.wikipedia.org/wiki/Auxigro" title="Auxigro" >Auxigro</a> is a plant growth preparation that contains 30% glutamic acid.</p>

<h3 >]NMR Spectroscopy</h3>

<p >In recent years, there has been much research into the use of <a href="http://en.wikipedia.org/wiki/Residual_dipolar_coupling" title="Residual dipolar coupling" >RDCs</a> in <a href="http://en.wikipedia.org/wiki/Nuclear_magnetic_resonance_spectroscopy" title="Nuclear magnetic resonance spectroscopy" >NMR spectroscopy</a>. A glutamic acid derivative, <a href="http://en.wikipedia.org/w/index.php?title=Poly-%CE%B3-benzyl-L-glutamate&action=edit&redlink=1" class="new" title="Poly-γ-benzyl-L-glutamate (page does not exist)" >poly-γ-benzyl-L-glutamate</a> (PBLG), is often used as an alignment medium to control the scale of the dipolar interactions observed.<sup id="cite_ref-22" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-22" >[23]</a></sup></p>

<h2 >Production</h2>

<p >China-based <a href="http://en.wikipedia.org/wiki/Fufeng_Group" title="Fufeng Group" >Fufeng Group</a> 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.</p>

<h2 >Pharmacology</h2>

<p >The drug <a href="http://en.wikipedia.org/wiki/Phencyclidine" title="Phencyclidine" >phencyclidine</a> (more commonly known as PCP) <a href="http://en.wikipedia.org/wiki/Receptor_antagonist" title="Receptor antagonist" >antagonizes</a> glutamic acid non-competitively at the NMDA receptor. For the same reasons, sub-anaesthetic doses of <a href="http://en.wikipedia.org/wiki/Ketamine" title="Ketamine" >ketamine</a> have strong dissociative and hallucinogenic effects. </p>

<p>

Glutamate does not easily pass the <a href="http://en.wikipedia.org/wiki/Blood_brain_barrier" title="Blood brain barrier" class="mw-redirect" >blood brain barrier</a>, but, instead, is transported by a high-affinity transport system.<sup id="cite_ref-23" class="reference" ><a href="http://en.wikipedia.org/wiki/Glutamic_acid#cite_note-23" >[24]</a></sup> It can also be converted into <a href="http://en.wikipedia.org/wiki/Glutamine" title="Glutamine" >glutamine</a>.

 </p>