Glutamate: Difference between revisions

Line 12:

==Chemistry==

~~Glutamate~~ generally exists as a negatively-charged carboxylate at pH values above 4.

In solutions, glutamate generally exists as a overall negatively-charged carboxylate at pH values above 4. As with other amino acids, it carries both a negatively charged carboxylate group and a positively charged amine, and its side chain has an additional carboxylate, giving it overall charge of -1 if completely ionised. It is one of the 20 proteogenic amino acids that serve as basic components of all proteins. Like all others, glutamate is an alpha amino acid, which means that its amine group is on the carbon that neighbors the carboxylic group, and an L-amino acid, referring to its "left handed" stereochemistry (in the more precise S/R naming system it would be (S)) <ref> Kennely P. J. and Rodwell, V. W, Amino Acids & Peptides (2018). In Harper's Illustrated Biochemistry, pp 14-22, LANGE</ref>.

In humans, glutamate is synthetised from alfa-keto glutarate, thus it is a non-essential amino acid. It is also a precursor for another amino acid, glutamine.

Because of its role as a neurotransmitter, glutamate concentration in the brain must be strictly regulated. It cannot easily cross the [[blood-brain barrier]] and most of it is synthetised de novo in brain cells and transported in the form of glutamine <ref>Hawkins RA. The blood-brain barrier and glutamate. Am J Clin Nutr. 2009 Sep;90(3):867S-874S. doi: 10.3945/ajcn.2009.27462BB. Epub 2009 Jul 1. PMID: 19571220; PMCID: PMC3136011.</ref>.

==Glutamate system==

There are two categories of glutamate receptors, named for the mechanism that gives rise to the postsynaptic current; ionotropic and metabotropic. Ionotropic receptors work via the movement of ions in and out on ligand-gated ion channels. Metabotropic receptors work via their activation of secondary messenger chemicals. These chemicals eventually induce the postsynaptic current, either through their own action or by activating the ligand-gated ion channels.

Line 21:

Line 23:

*'''Agonists'''

A glutamate [[agonist]] is a chemical that binds to and activates a glutamate [[receptor]] and triggers a response, displaying full efficacy at that receptor. An example of this is [[theanine]], a weak agonist of the NMDA receptor.<ref name="WakabayashiNumakawa2011">{{cite journal|last1=Wakabayashi|first1=Chisato|last2=Numakawa|first2=Tadahiro|last3=Ninomiya|first3=Midori|last4=Chiba|first4=Shuichi|last5=Kunugi|first5=Hiroshi|title=Behavioral and molecular evidence for psychotropic effects in l-theanine|journal=Psychopharmacology|volume=219|issue=4|year=2011|pages=1099–1109|issn=0033-3158|doi=10.1007/s00213-011-2440-z}}</ref>

A glutamate [[agonist]] is a chemical that binds to and activates a glutamate [[receptor]] and triggers a response, displaying full efficacy at that receptor. An example of this is [[theanine]], a weak agonist of the NMDA receptor.<ref name="WakabayashiNumakawa2011">{{cite journal|last1=Wakabayashi|first1=Chisato|last2=Numakawa|first2=Tadahiro|last3=Ninomiya|first3=Midori|last4=Chiba|first4=Shuichi|last5=Kunugi|first5=Hiroshi|title=Behavioral and molecular evidence for psychotropic effects in l-theanine|journal=Psychopharmacology|volume=219|issue=4|year=2011|pages=1099–1109|issn=0033-3158|doi=10.1007/s00213-011-2440-z}}</ref>. Because of the high expression and excitatory effects, NMDA receptor overactivation can cause seizures. Stronger agonists are therefore often pro-convulsant and neurotoxic <ref>Hanada T. Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors. Biomolecules. 2020 Mar 18;10(3):464. doi: 10.3390/biom10030464. PMID: 32197322; PMCID: PMC7175173.</ref>.

*'''Positive Allosteric Modulators'''

@@ Line 12: / Line 12: @@
 ==Chemistry==
-Glutamate generally exists as a negatively-charged carboxylate at pH values above 4.
+In solutions, glutamate generally exists as a overall negatively-charged carboxylate at pH values above 4. As with other amino acids, it carries both a negatively charged carboxylate group and a positively charged amine, and its side chain has an additional carboxylate, giving it overall charge of -1 if completely ionised. It is one of the 20 proteogenic amino acids that serve as basic components of all proteins. Like all others, glutamate is an alpha amino acid, which means that its amine group is on the carbon that neighbors the carboxylic group, and an L-amino acid, referring to its "left handed" stereochemistry (in the more precise S/R naming system it would be (S)) <ref> Kennely P. J. and Rodwell, V. W, Amino Acids & Peptides (2018). In Harper's Illustrated Biochemistry, pp 14-22, LANGE</ref>.
+In humans, glutamate is synthetised from alfa-keto glutarate, thus it is a non-essential amino acid. It is also a precursor for another amino acid, glutamine.
+Because of its role as a neurotransmitter, glutamate concentration in the brain must be strictly regulated. It cannot easily cross the [[blood-brain barrier]] and most of it is synthetised de novo in brain cells and transported in the form of glutamine <ref>Hawkins RA. The blood-brain barrier and glutamate. Am J Clin Nutr. 2009 Sep;90(3):867S-874S. doi: 10.3945/ajcn.2009.27462BB. Epub 2009 Jul 1. PMID: 19571220; PMCID: PMC3136011.</ref>.
 ==Glutamate system==
 There are two categories of glutamate receptors, named for the mechanism that gives rise to the postsynaptic current; ionotropic and metabotropic. Ionotropic receptors work via the movement of ions in and out on ligand-gated ion channels. Metabotropic receptors work via their activation of secondary messenger chemicals. These chemicals eventually induce the postsynaptic current, either through their own action or by activating the ligand-gated ion channels.
@@ Line 21: / Line 23: @@
 *'''Agonists'''
-A glutamate [[agonist]] is a chemical that binds to and activates a glutamate [[receptor]] and triggers a response, displaying full efficacy at that receptor. An example of this is [[theanine]], a weak agonist of the NMDA receptor.<ref name="WakabayashiNumakawa2011">{{cite journal|last1=Wakabayashi|first1=Chisato|last2=Numakawa|first2=Tadahiro|last3=Ninomiya|first3=Midori|last4=Chiba|first4=Shuichi|last5=Kunugi|first5=Hiroshi|title=Behavioral and molecular evidence for psychotropic effects in l-theanine|journal=Psychopharmacology|volume=219|issue=4|year=2011|pages=1099–1109|issn=0033-3158|doi=10.1007/s00213-011-2440-z}}</ref>
+A glutamate [[agonist]] is a chemical that binds to and activates a glutamate [[receptor]] and triggers a response, displaying full efficacy at that receptor. An example of this is [[theanine]], a weak agonist of the NMDA receptor.<ref name="WakabayashiNumakawa2011">{{cite journal|last1=Wakabayashi|first1=Chisato|last2=Numakawa|first2=Tadahiro|last3=Ninomiya|first3=Midori|last4=Chiba|first4=Shuichi|last5=Kunugi|first5=Hiroshi|title=Behavioral and molecular evidence for psychotropic effects in l-theanine|journal=Psychopharmacology|volume=219|issue=4|year=2011|pages=1099–1109|issn=0033-3158|doi=10.1007/s00213-011-2440-z}}</ref>. Because of the high expression and excitatory effects, NMDA receptor overactivation can cause seizures. Stronger agonists are therefore often pro-convulsant and neurotoxic <ref>Hanada T. Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors. Biomolecules. 2020 Mar 18;10(3):464. doi: 10.3390/biom10030464. PMID: 32197322; PMCID: PMC7175173.</ref>.
 *'''Positive Allosteric Modulators'''