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Record Information
Version1.0
Created at2005-11-16 15:48:42 UTC
Updated at2020-11-24 22:18:49 UTC
NP-MRD IDNP0000852
Secondary Accession NumbersNone
Natural Product Identification
Common NameKynurenic acid
DescriptionKynurenic acid (KYNA) is a well-known endogenous antagonist of the glutamate ionotropic excitatory amino acid receptors N-methyl-D-aspartate (NMDA), alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate receptors and of the nicotine cholinergic subtype alpha 7 receptors. KYNA neuroprotective and anticonvulsive activities have been demonstrated in animal models of neurodegenerative diseases. Because of KYNA's neuromodulatory character, its involvement has been speculatively linked to the pathogenesis of a number of neurological conditions including those in the ageing process. Different patterns of abnormalities in various stages of KYNA metabolism in the CNS have been reported in Alzheimer's disease, Parkinson's disease and Huntington's disease. In HIV-1-infected patients and in patients with Lyme neuroborreliosis a marked rise of KYNA metabolism was seen. In the ageing process KYNA metabolism in the CNS of rats shows a characteristic pattern of changes throughout the life span. A marked increase of the KYNA content in the CNS occurs before the birth, followed by a dramatic decline on the day of birth. A low activity was seen during ontogenesis, and a slow and progressive enhancement occurs during maturation and ageing. This remarkable profile of KYNA metabolism alterations in the mammalian brain has been suggested to result from the development of the organisation of neuronal connections and synaptic plasticity, development of receptor recognition sites, maturation and ageing. There is significant evidence that KYNA can improve cognition and memory, but it has also been demonstrated that it interferes with working memory. Impairment of cognitive function in various neurodegenerative disorders is accompanied by profound reduction and/or elevation of KYNA metabolism. The view that enhancement of CNS KYNA levels could underlie cognitive decline is supported by the increased KYNA metabolism in Alzheimer's disease, by the increased KYNA metabolism in down's syndrome and the enhancement of KYNA function during the early stage of Huntington's disease. Kynurenic acid is the only endogenous N-methyl-D-aspartate (NMDA) receptor antagonist identified up to now, that mediates glutamatergic hypofunction. Schizophrenia is a disorder of dopaminergic neurotransmission, but modulation of the dopaminergic system by glutamatergic neurotransmission seems to play a key role. Despite the NMDA receptor antagonism, kynurenic acid also blocks, in lower doses, the nicotinergic acetycholine receptor, i.E., Increased kynurenic acid levels can explain psychotic symptoms and cognitive deterioration. Kynurenic acid levels are described to be higher in the cerebrospinal fluid (CSF) and in critical central nervous system (CNS) regions of schizophrenics as compared to controls. (PMID: 17062375 , 16088227 ).
Structure
Thumb
Synonyms
ValueSource
4-Hydroxy-2-chinolincarbonsaeureChEBI
4-Hydroxy-2-quinolinecarboxylic acidChEBI
4-Hydroxyquinaldic acidChEBI
4-Hydroxyquinaldinic acidChEBI
KynurenateChEBI
KynurensaeureChEBI
4-Hydroxy-2-quinolinecarboxylateGenerator
4-HydroxyquinaldateGenerator
4-HydroxyquinaldinateGenerator
2-Carboxy-4-hydroxyquinolineHMDB
4-Hydroxy-quinaldateHMDB
4-Hydroxy-quinaldic acidHMDB
4-Hydroxyquinoline-2-carboxylateHMDB
4-Hydroxyquinoline-2-carboxylic acidHMDB
Quinurenic acidHMDB
Acid, kynurenicHMDB
Chemical FormulaC10H7NO3
Average Mass189.1675 Da
Monoisotopic Mass189.04259 Da
IUPAC Name4-oxo-1,4-dihydroquinoline-2-carboxylic acid
Traditional Nameacid, kynurenic
CAS Registry Number492-27-3
SMILES
OC(=O)C1=CC(=O)C2=CC=CC=C2N1
InChI Identifier
InChI=1S/C10H7NO3/c12-9-5-8(10(13)14)11-7-4-2-1-3-6(7)9/h1-5H,(H,11,12)(H,13,14)
InChI KeyHCZHHEIFKROPDY-UHFFFAOYSA-N
Spectra
Spectrum TypeDescriptionDepositor IDDeposition DateView
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Wishart Lab2021-06-20View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Wishart Lab2021-06-20View Spectrum
Species
Species of Origin
Species NameSourceReference
Ephedra pachyclada ssp.sinaicaKNApSAcK Database
Tripterygium wilfordiiKNApSAcK Database
Species Where Detected
Species NameSourceReference
Homo sapiens (Urine)KNApSAcK Database
Chemical Taxonomy
Description Belongs to the class of organic compounds known as quinoline carboxylic acids. These are quinolines in which the quinoline ring system is substituted by a carboxyl group at one or more positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassQuinoline carboxylic acids
Direct ParentQuinoline carboxylic acids
Alternative Parents
Substituents
  • Quinoline-2-carboxylic acid
  • Dihydroquinolone
  • Dihydroquinoline
  • Pyridine carboxylic acid
  • Pyridine carboxylic acid or derivatives
  • Pyridine
  • Benzenoid
  • Heteroaromatic compound
  • Vinylogous amide
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Azacycle
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point280 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.95 g/LALOGPS
logP10(1.16) g/LALOGPS
logP10(1.58) g/LChemAxon
logS10(-2.3) g/LALOGPS
pKa (Strongest Acidic)3.17ChemAxon
pKa (Strongest Basic)-4.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area66.4 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity52.32 m³·mol⁻¹ChemAxon
Polarizability18.05 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
HMDB IDHMDB0000715
DrugBank IDDB11937
Phenol Explorer Compound IDNot Available
FoodDB IDFDB022200
KNApSAcK IDC00026453
Chemspider ID3712
KEGG Compound IDC01717
BioCyc IDKYNURENATE
BiGG ID38234
Wikipedia LinkKynurenic_acid
METLIN ID5683
PubChem Compound3845
PDB IDNot Available
ChEBI ID18344
Good Scents IDNot Available
References
General References
  1. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [PubMed:19212411 ]
  2. Medana IM, Hien TT, Day NP, Phu NH, Mai NT, Chu'ong LV, Chau TT, Taylor A, Salahifar H, Stocker R, Smythe G, Turner GD, Farrar J, White NJ, Hunt NH: The clinical significance of cerebrospinal fluid levels of kynurenine pathway metabolites and lactate in severe malaria. J Infect Dis. 2002 Mar 1;185(5):650-6. Epub 2002 Feb 14. [PubMed:11865422 ]
  3. Medana IM, Day NP, Salahifar-Sabet H, Stocker R, Smythe G, Bwanaisa L, Njobvu A, Kayira K, Turner GD, Taylor TE, Hunt NH: Metabolites of the kynurenine pathway of tryptophan metabolism in the cerebrospinal fluid of Malawian children with malaria. J Infect Dis. 2003 Sep 15;188(6):844-9. Epub 2003 Sep 9. [PubMed:12964115 ]
  4. Heyes MP, Saito K, Crowley JS, Davis LE, Demitrack MA, Der M, Dilling LA, Elia J, Kruesi MJ, Lackner A, et al.: Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain. 1992 Oct;115 ( Pt 5):1249-73. [PubMed:1422788 ]
  5. Parada-Turska J, Rzeski W, Zgrajka W, Majdan M, Kandefer-Szerszen M, Turski W: Kynurenic acid, an endogenous constituent of rheumatoid arthritis synovial fluid, inhibits proliferation of synoviocytes in vitro. Rheumatol Int. 2006 Mar;26(5):422-6. Epub 2005 Oct 12. [PubMed:16220290 ]
  6. Amirkhani A, Heldin E, Markides KE, Bergquist J: Quantitation of tryptophan, kynurenine and kynurenic acid in human plasma by capillary liquid chromatography-electrospray ionization tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Nov 25;780(2):381-7. [PubMed:12401365 ]
  7. Ilzecka J, Kocki T, Stelmasiak Z, Turski WA: Endogenous protectant kynurenic acid in amyotrophic lateral sclerosis. Acta Neurol Scand. 2003 Jun;107(6):412-8. [PubMed:12757473 ]
  8. Bapurao S, Krishnaswamy K: Vitamin B6 nutritional status of pellagrins and their leucine tolerance. Am J Clin Nutr. 1978 May;31(5):819-24. [PubMed:206127 ]
  9. Nilsson LK, Nordin C, Jonsson EG, Engberg G, Linderholm KR, Erhardt S: Cerebrospinal fluid kynurenic acid in male and female controls - correlation with monoamine metabolites and influences of confounding factors. J Psychiatr Res. 2007 Jan-Feb;41(1-2):144-51. Epub 2006 Jan 24. [PubMed:16434056 ]
  10. Milart P, Sikorski R: [Kynurenic acid concentration in blood and urine during normal pregnancy]. Ginekol Pol. 1998 Dec;69(12):968-73. [PubMed:10224760 ]
  11. Moroni F, Russi P, Lombardi G, Beni M, Carla V: Presence of kynurenic acid in the mammalian brain. J Neurochem. 1988 Jul;51(1):177-80. [PubMed:3379401 ]
  12. Turski WA, Nakamura M, Todd WP, Carpenter BK, Whetsell WO Jr, Schwarcz R: Identification and quantification of kynurenic acid in human brain tissue. Brain Res. 1988 Jun 28;454(1-2):164-9. [PubMed:3409000 ]
  13. Connick JH, Carla V, Moroni F, Stone TW: Increase in kynurenic acid in Huntington's disease motor cortex. J Neurochem. 1989 Mar;52(3):985-7. [PubMed:2521895 ]
  14. Swartz KJ, Matson WR, MacGarvey U, Ryan EA, Beal MF: Measurement of kynurenic acid in mammalian brain extracts and cerebrospinal fluid by high-performance liquid chromatography with fluorometric and coulometric electrode array detection. Anal Biochem. 1990 Mar;185(2):363-76. [PubMed:2339792 ]
  15. Baran H, Cairns N, Lubec B, Lubec G: Increased kynurenic acid levels and decreased brain kynurenine aminotransferase I in patients with Down syndrome. Life Sci. 1996;58(21):1891-9. [PubMed:8637415 ]
  16. Beal MF, Matson WR, Storey E, Milbury P, Ryan EA, Ogawa T, Bird ED: Kynurenic acid concentrations are reduced in Huntington's disease cerebral cortex. J Neurol Sci. 1992 Mar;108(1):80-7. [PubMed:1385624 ]
  17. Kepplinger B, Baran H, Kainz A, Ferraz-Leite H, Newcombe J, Kalina P: Age-related increase of kynurenic acid in human cerebrospinal fluid - IgG and beta2-microglobulin changes. Neurosignals. 2005;14(3):126-35. [PubMed:16088227 ]
  18. Muller N, Schwarz M: Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission. Neurotox Res. 2006 Oct;10(2):131-48. [PubMed:17062375 ]