Kynurenic acid

Kynurenic acid
IUPAC name

4-hydroxyquinoline-2-carboxylic acid
Other names

Kinurenic acid, kynuronic acid, quinurenic acid, transtorine
Identifiers
CAS number 492-27-3 Y
PubChem 3845
ChemSpider 3712 Y
KEGG C01717 Y
ChEBI CHEBI:18344 N
ChEMBL CHEMBL299155 Y
Jmol-3D images Image 1
Properties
Molecular formula C10H7N1O3
Molar mass 189.168 g/mol
Melting point

282.5°C
 N (verify) (what is: Y/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Kynurenic acid (KYNA) is a product of the normal metabolism of amino acid L-tryptophan. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant, most likely through acting as an antagonist at excitatory amino acid receptors. Because of this activity, it may influence important neurophysiologic and neuropathologic processes. As a result, kynurenic acid has been considered for use in therapy in certain neurobiological disorders. Conversely, increased levels of kynurenic acid have also been linked to certain pathological conditions.

Kynurenic acid was discovered in 1853 by the German chemist Justus von Liebig in dog urine, which it was apparently named after.[1]

It is formed from L-kynurenine in a reaction catalyzed by the enzyme kynurenine—oxoglutarate transaminase.

Contents

Mechanism of action

KYNA has been found to act on three receptors:

Role in disease

High levels of kynurenic acid have been identified in patients suffering from tick-borne encephalitis, schizophrenia and HIV-related illnesses. In all these situations increased levels were associated with confusion and psychotic symptoms. Kynurenic acid acts in the brain as a glycine-site NMDAr antagonist, key in glutamatergic neurotransmission system, which is thought to be involved in the pathophysiology and pathogenesis of schizophrenia.

A kynurenic acid hypothesis of schizophrenia has been proposed in 2007,[5][6] based on its action on midbrain dopamine activity and NMDArs, thus linking dopamine hypothesis of schizophrenia with the glutamate hypothesis of the disease.

High levels of kynurenic acid have been identified in human urine in certain metabolic disorders, such as marked pyridoxine deficiency and deficiency/absence of kynureninase.

When researchers decreased the levels of kynurenic acid in the brains of mice, the cognition was shown to improve markedly. [7]

See also

References

  1. ^ Liebig, J., Uber Kynurensäure, Justus Liebigs Ann. Chem., 86: 125-126, 1853.
  2. ^ Dobelis P., Varnell A., and Cooper, D.C. (2011). "Nicotinic α7 acetylcholine receptor-mediated currents are not modulated by the tryptophan metabolite kynurenic acid in adult hippocampal interneurons". Nature Precedings. doi:10.1038/npre.2011.6277.1. http://www.neuro-cloud.net/nature-precedings/dobelis/. >
  3. ^ Grilli M, Raiteri L, Patti L, Parodi M, Robino F, Raiteri M, Marchi M (2006). "Modulation of the function of presynaptic α7 and non-α7 nicotinic receptors by the tryptophan metabolites, 5-hydroxyindole and kynurenate in mouse brain". Br. J. Pharmacol. 149 (6): 724–32. doi:10.1038/sj.bjp.0706914. PMC 2014664. PMID 17016503. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2014664. 
  4. ^ Wang J, Simonavicius N, Wu X, Swaminath G, Reagan J, Tian H, Ling L (2006). "Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35". J. Biol. Chem. 281 (31): 22021–8. doi:10.1074/jbc.M603503200. PMID 16754668. 
  5. ^ Erhardt S, Schwieler L, Nilsson L, Linderholm K, Engberg G (2007). "The kynurenic acid hypothesis of schizophrenia". Physiol. Behav. 92 (1–2): 203–9. doi:10.1016/j.physbeh.2007.05.025. PMID 17573079. 
  6. ^ Erhardt S, Schwieler L, Engberg G (2003). "Kynurenic acid and schizophrenia". Adv. Exp. Med. Biol. 527: 155–65. PMID 15206728. 
  7. ^ Robert Schwarcz; Elmer, Greg I; Bergeron, Richard; Albuquerque, Edson X; Guidetti, Paolo; Wu, Hui-Qiu; Schwarcz, Robert (2010). "Reduction of Endogenous Kynurenic Acid Formation Enhances Extracellular Glutamate, Hippocampal Plasticity, and Cognitive Behavior". Neuropsychopharmacology 35 (8): 1734–1742. doi:10.1038/npp.2010.39. PMC 3055476. PMID 20336058. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3055476. 

External links

Amino acids

Alanine · Aspartate · Cycloserine · DMG · GABA · Glutamate · Glycine · Hypotaurine · Kynurenic acid (Transtorine) · NAAG (Spaglumic acid) · NMG (Sarcosine) · Serine · Taurine · TMG (Betaine)
Endocannabinoids
Gasotransmitters
Monoamines
Purines

Adenosine · ADP · AMP · ATP
Trace amines
Others
See also Template:Neuropeptides

M: PNS

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