Kainic acid

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"Kainate" redirects here. Not to be confused with Kainite.
Kainic acid
Stereo, skeletal formula of kainic acid
Names
IUPAC name
(3S,4S)-3-(Carboxymethyl)-4-(prop-1-en-2-yl)-L-proline
Systematic IUPAC name
(2S,3S,4S)-3-(Carboxymethyl)-4-(prop-1-en-2-yl)pyrrolidine-2-carboxylic acid
Other names
2-Carboxy-3-carboxymethyl-4-isopropenyl-pyrrolidine[citation needed]
Identifiers
3D model (
JSmol
)
86660
ChEBI
ChEMBL
ChemSpider
KEGG
MeSH Kainic+acid
UNII
  • InChI=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) ☒N
    Key: VLSMHEGGTFMBBZ-UHFFFAOYSA-N ☒N
  • OC(=O)[C@H]1NC[C@H](C(C)=C)[C@@H]1CC(=O)O
Properties
C10H15NO4
Molar mass 213.233 g·mol−1
Melting point 215 °C (419 °F; 488 K) (decomposes)
log P 0.635
Acidity (pKa) 2.031
Basicity (pKb) 11.966
Structure
Monoclinic
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Kainic acid, or kainate, is an acid that naturally occurs in some

metabotropic glutamate receptors. Kainic acid is an agonist for kainate receptors, a type of ionotropic glutamate receptor. Kainate receptors likely control a sodium channel that produces excitatory postsynaptic potentials (EPSPs) when glutamate binds.[1]

Kainic acid is commonly injected into laboratory animal models to study the effects of

excitotoxic 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.[2] In fact, kainate seems to regulate serotonergic activity in the vertebrate retina.[3]

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

lesions potentially cause additional damage to the brain due to the very nature of the inserted electrode or cannula. Therefore, the most effective ablation studies
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.

Biosynthesis

In 2019, Chekan et al. were able to use bioinformatic tools to look for domoic acid gene homologs in the seaweed Digenea simplex.[4] 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.

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.

Biosynthesis of kainic acid and kainic acid lactone

Occurrence

Kainic acid was originally isolated from the

seaweeds Digenea simplex and Chondria armata in 1953.[5] They are called "Kainin-sou" or "Makuri" in Japan, and are used as an anthelmintic
.

Pharmacological activity

Kainic acid is utilised in primary neuronal cell cultures[6] and in the acute brain slice preparation[7] to study the physiological effect of excitotoxicity and assess the neuroprotective capabilities of potential therapeutics.

Kainic acid is a potent

GluK2 subunit and also through activation of AMPA receptors, for which it serves as a partial agonist.[10] 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.[11]

Applications

See also

References

  1. ISBN 978-0-205-23939-9
    .
  2. ISBN 978-0-205-23939-9
    .
  3. S2CID 254384979
    .
  4. PMID 30995339
    .
  5. PMID 9586226
    .
  6. S2CID 42116946
    .
  7. ISBN 978-1-4939-0380-1
    .
  8. OCLC 53634796
    .
  9. PMID 22787646
    .
  10. PMID 24760837
    .
  11. doi:10.1021/cen-v078n001.p014
    . Retrieved 22 February 2021.
  12. OCLC 53634796
    .

External links