| Revision as of 07:16, 18 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,044 edits Saving copy of the {{chembox}} taken from revid 469809974 of page Kainic_acid for the Chem/Drugbox validation project (updated: 'ChEMBL', 'KEGG', 'StdInChI', 'StdInChIKey'). |
Latest revision as of 10:58, 18 October 2023 edit Wikipedialuva (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers, Rollbackers39,614 editsm clean up, typo(s) fixed: et al → et al. (2)Tag: AWB |
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{{Redirect-distinguish|Kainate|Kainite}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Chembox |
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{{Chembox |
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| Verifiedfields = changed |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 461783508 |
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| verifiedrevid = 477496607 |
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| ImageFile = Kainic acid.png |
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| ImageFile = Kainic acid.png |
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| ImageFile_Ref = {{chemboximage|correct|??}} |
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| ImageFile_Ref = {{chemboximage|correct|??}} |
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| ImageSize = 200px |
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| ImageSize = 200px |
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| ImageName = Stereo, skeletal formula of kainic acid ((2S,3S,4S)-3-methyl,-4-prop-1-en-2-yl,-2-carboxylic acid) |
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| ImageName = Stereo, skeletal formula of kainic acid |
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| IUPACName = (2''S'',3''S'',4''S'')-3-(Carboxymethyl)-4-prop-1-en-2-ylpyrrolidine-2-carboxylic acid<ref>{{PubChem|10255}}</ref> |
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| IUPACName = (3''S'',4''S'')-3-(Carboxymethyl)-4-(prop-1-en-2-yl)-<small>L</small>-proline |
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| OtherNames = (3''S'',4''S'')-3-(Carboxymethyl)-4-prop-1-en-2-yl-<small>L</small>-proline; 2-Carboxy-3-carboxymethyl-4-isopropenyl-pyrrolidine{{Citation needed|date = May 2011}} |
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| SystematicName = (2''S'',3''S'',4''S'')-3-(Carboxymethyl)-4-(prop-1-en-2-yl)pyrrolidine-2-carboxylic acid |
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| OtherNames = 2-Carboxy-3-carboxymethyl-4-isopropenyl-pyrrolidine{{Citation needed|date = May 2011}} |
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| Section1 = {{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| CASNo = 487-79-6 |
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| CASNo = 487-79-6 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| PubChem = 10255 |
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| PubChem = 10255 |
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| ChemSpiderID = 9837 |
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| PubChem_Ref = {{Pubchemcite|correct|pubchem}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 9837 |
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| UNII = SIV03811UC |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = SIV03811UC |
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| KEGG = C12819 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG = <!-- blanked - oldvalue: C12819 --> |
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| MeSHName = Kainic+acid |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| MeSHName = Kainic+acid |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 31746 |
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| ChEBI = 31746 |
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| ChEMBL = 275040 |
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| ChEMBL = 27527 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| Beilstein = 86660 |
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| Beilstein = 86660 |
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| SMILES = CC(=C)1CN(1CC(=O)O)C(=O)O |
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| SMILES = OC(=O)1NC(C(C)=C)1CC(=O)O |
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| StdInChI = 1S/C10H15NO4/c1-5(2)7-4-11-9(10(14)15)6(7)3-8(12)13/h6-7,9,11H,1,3-4H2,2H3,(H,12,13)(H,14,15)/t6-,7+,9-/m0/s1 |
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| StdInChI = 1S/C10H15NO4/c1-5(2)7-4-11-9(10(14)15)6(7)3-8(12)13/h6-7,9,11H,1,3-4H2,2H3,(H,12,13)(H,14,15) |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = VLSMHEGGTFMBBZ-OOZYFLPDSA-N |
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| StdInChIKey = VLSMHEGGTFMBBZ-UHFFFAOYSA-N |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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}} |
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}} |
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| Section2 = {{Chembox Properties |
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|Section2={{Chembox Properties |
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| C=10|H=15|N=1|O=4 |
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| C=10 | H=15 | N=1 | O=4 |
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| MeltingPtC = 215 |
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| ExactMass = 213.100107973 g mol<sup>-1</sup> |
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| MeltingPt_notes = (decomposes) |
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| MeltingPtC = 215 |
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| LogP = 0.635 |
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| Melting_notes = decomposes |
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| LogP = 0.635 |
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| pKa = 2.031 |
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| pKa = 2.031 |
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| pKb = 11.966 |
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| pKb = 11.966 |
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| Section3 = {{Chembox Structure |
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|Section3={{Chembox Structure |
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| CrystalStruct = Monoclinic |
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| CrystalStruct = Monoclinic |
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'''Kainic acid''', or '''kainate''', is an acid that naturally occurs in some ]. Kainic acid is a potent neuroexcitatory amino acid ] that acts by activating receptors for ], the principal excitatory ] in the central nervous system. Glutamate is produced by the cell's metabolic processes and there are four major classifications of ]: ] receptors, ] receptors, kainate receptors, and the ]. Kainic acid is an agonist for ]s, a type of ]. Kainate receptors likely control a ] that produces ]s (EPSPs) when glutamate binds.<ref>{{cite book| vauthors = Carlson NR |title=Physiology of Behavior|url=https://archive.org/details/physiologybehavi00carl_811|url-access=limited|publisher=Pearson|isbn=978-0-205-23939-9|pages=|year=2013}}</ref> |
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Kainic acid is commonly injected into laboratory animal models to study the effects of ]. Kainic acid is a direct agonist of the glutamic kainate receptors and large doses of concentrated solutions produce immediate neuronal death by overstimulating neurons to death. Such damage and death of neurons is referred to as an ] lesion. Thus, in large, concentrated doses kainic acid can be considered a neurotoxin, and in small doses of dilute solution kainic acid will chemically stimulate neurons.<ref>{{cite book | vauthors = Carlson NR |title=Physiology of Behavior|url=https://archive.org/details/physiologybehavi00carl_811|url-access=limited|publisher=Pearson|isbn=978-0-205-23939-9|pages=|year=2013}}</ref> In fact, kainate seems to regulate serotonergic activity in the vertebrate retina.<ref>{{cite journal | vauthors = Passos AD, Herculano AM, Oliveira KR, de Lima SM, Rocha FA, Freitas HR, da Silva Sampaio L, Figueiredo DP, da Costa Calaza K, de Melo Reis RA, do Nascimento JL | display-authors = 6 | title = Regulation of the Serotonergic System by Kainate in the Avian Retina | journal = Cellular and Molecular Neurobiology | volume = 39 | issue = 7 | pages = 1039–1049 | date = October 2019 | pmid = 31197744 | doi = 10.1007/s10571-019-00701-8 | s2cid = 254384979 }}</ref> |
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Electrical stimulation of designated areas of the brain are generally administered by passing an electric current through a wire that is inserted into the brain to lesion a particular area of the brain. Electrical stimulation indiscriminately destroys anything in the vicinity of the electrode tip, including neural bodies and axons of neurons passing through; therefore it is difficult to attribute the effects of the lesion to a single area. Chemical stimulation is typically administered through a cannula that is inserted into the brain via ]. Chemical stimulation, while more complicated than electrical stimulation, has the distinct advantage of activating cell bodies, but not nearby axons, because only cell bodies and subsequent dendrites contain glutamate receptors. Therefore, chemical stimulation by kainic acid is more localized than electrical stimulation. Both chemical and electrical ] potentially cause additional damage to the brain due to the very nature of the inserted electrode or cannula. Therefore, the most effective ] are performed in comparison to a sham lesion that duplicates all the steps of producing a brain lesion except the one that actually causes the brain damage, that is, injection of kainic acid or administration of an electrical shock. |
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== Biosynthesis == |
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In 2019, Chekan et al. were able to use bioinformatic tools to look for domoic acid gene homologs in the seaweed ''Digenea simplex''.<ref>{{cite journal | vauthors = Chekan JR, McKinnie SM, Moore ML, Poplawski SG, Michael TP, Moore BS | title = Scalable Biosynthesis of the Seaweed Neurochemical, Kainic Acid | journal = Angewandte Chemie | volume = 58 | issue = 25 | pages = 8454–8457 | date = June 2019 | pmid = 30995339 | pmc = 6574125 | doi = 10.1002/anie.201902910 }}</ref> Researchers identified a cluster containing genes identified as the kainic acid biosynthesis (''kab'') genes. This cluster contains an annotated N-prenyltransferase, α-ketoglutarate (αKG)-dependent dioxygenase, and several retrotransposable elements. To confirm production of kainic acid through the identified cluster, Chekan et al. expressed the genes in ''Escherichia'' coli and validated the enzymatic functions of each proposed gene. |
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The first step of the pathway involves the N-prenyltransferase, KabA, which allows for the prenylation of L-glutamic acid with dimethylallyl pyrophosphate (DMAPP) to form the intermediate ''N''-dimethylallyl-l-glutamic acid (prekainic acid). KabC then catalyzes the stereocontrolled formation of the trisubstituted pyrrolidine ring, taking prekainic acid to the final kainic acid. KabC was also able to produce another kainic acid isomer, kainic acid lactone. |
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==Occurrence== |
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Kainic acid was originally isolated from the ] '']'' and '']'' in 1953.<ref>{{cite journal | vauthors = Moloney MG | title = Excitatory amino acids | journal = Natural Product Reports | volume = 15 | issue = 2 | pages = 205–219 | date = April 1998 | pmid = 9586226 | doi = 10.1039/a815205y }}</ref> They are called "Kainin-sou" or "Makuri" in ], and are used as an ]. |
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==Pharmacological activity== |
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Kainic acid is utilised in primary neuronal cell cultures<ref>{{cite journal | vauthors = Meade AJ, Meloni BP, Mastaglia FL, Watt PM, Knuckey NW | title = AP-1 inhibitory peptides attenuate in vitro cortical neuronal cell death induced by kainic acid | journal = Brain Research | volume = 1360 | pages = 8–16 | date = November 2010 | pmid = 20833150 | doi = 10.1016/j.brainres.2010.09.007 | s2cid = 42116946 }}</ref> and in the acute brain slice preparation<ref>{{cite book| vauthors = Craig AJ, Housley GD, Fath T | chapter = Modeling excitotoxic ischemic brain injury of cerebellar Purkinje neurons by intravital and in vitro multi-photon laser scanning microscopy. | veditors = Bakota L, Brandt R | title = Laser scanning microscopy and quantitative image analysis of neuronal tissue. |date=2014|publisher=Springer|isbn=978-1-4939-0380-1|pages=105–128}}</ref> to study the physiological effect of excitotoxicity and assess the neuroprotective capabilities of potential therapeutics. |
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Kainic acid is a potent ] excitant that is used in epilepsy research to induce seizures in experimental animals,<ref>{{Cite book|title=A study of the changes in dentate granule cell excitability and inhibition in the kainic acid model of temporal lobe epilepsy.| vauthors = Barrow PA |oclc=53634796}}</ref> at a typical dose of 10–30 mg/kg in mice. In addition to inducing seizures, kainic acid is excitotoxic and epileptogenic.<ref>{{cite book | vauthors = Ben-Ari Y | chapter = Kainate and Temporal Lobe Epilepsies: 3 decades of progress | veditors = Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV | title=Jasper's Basic Mechanisms of the Epilepsies | edition=4th | location=Bethesda (MD) | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK98166/ |pmid = 22787646| year = 2012 | publisher = National Center for Biotechnology Information (US) }}</ref> Kainic acid induces seizures via activation of ]s containing the ] subunit and also through activation of AMPA receptors, for which it serves as a partial agonist.<ref>{{cite journal | vauthors = Fritsch B, Reis J, Gasior M, Kaminski RM, Rogawski MA | title = Role of GluK1 kainate receptors in seizures, epileptic discharges, and epileptogenesis | journal = The Journal of Neuroscience | volume = 34 | issue = 17 | pages = 5765–5775 | date = April 2014 | pmid = 24760837 | pmc = 3996208 | doi = 10.1523/JNEUROSCI.5307-13.2014 }}</ref> Also, infusion with kainic acid in the hippocampus of animals results in major damage of pyramidal neurons and subsequent seizure activity. Supply shortages beginning in 2000 have caused the cost of kainic acid to rise significantly.<ref>{{cite journal | vauthors = Tremblay JF |title=Shortage of kainic acid hampers neuroscience research |url=https://www.researchgate.net/publication/272136052 |journal=Chemical & Engineering News Archive |year=2000 |volume=78 |pages=14–15 |publisher=Chemical and Engineering News |doi=10.1021/cen-v078n001.p014 |access-date=22 February 2021}}</ref> |
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==Applications== |
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* ] research |
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** neurodegenerative agent |
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** modeling of ]<ref>{{Cite book|title=A study of the changes in dentate granule cell excitability and inhibition in the kainic acid model of temporal lobe epilepsy.| vauthors = Barrow PA |oclc=53634796}}</ref> |
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** modeling of ] |
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== See also == |
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* ] |
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* ] |
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* ] |
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== References == |
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{{Reflist|2}} |
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== External links == |
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{{Glutamate receptor modulators}} |
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{{Glutamate metabolism and transport modulators}} |
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{{Authority control}} |
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