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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-06-10 21:22:48 UTC
HMDB IDHMDB00715
Secondary Accession NumbersNone
Metabolite 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-oxo-1H-Quinoline-2-carboxylateGenerator
4-Hydroxy-2-quinolinecarboxylateGenerator
4-HydroxyquinaldateGenerator
4-HydroxyquinaldinateGenerator
Kynurenic acidGenerator
2-Carboxy-4-hydroxyquinolineHMDB
4-Hydroxy-quinaldateHMDB
4-Hydroxy-quinaldic acidHMDB
4-Hydroxyquinoline-2-carboxylateHMDB
4-Hydroxyquinoline-2-carboxylic acidHMDB
Quinurenic acidHMDB
Chemical FormulaC10H7NO3
Average Molecular Weight189.1675
Monoisotopic Molecular Weight189.042593095
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 KeyInChIKey=HCZHHEIFKROPDY-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound 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 or derivatives
  • Pyridine carboxylic acid
  • Benzenoid
  • Pyridine
  • Heteroaromatic compound
  • Vinylogous amide
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Cytoplasm
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 mg/mLALOGPS
logP1.16ALOGPS
logP1.58ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)3.17ChemAxon
pKa (Strongest Basic)-4.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area66.4 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity52.32 m3·mol-1ChemAxon
Polarizability18.05 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-0159-1985000000-f1c74ffc481c3d0faaa2View in MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0159-3895000000-6ba2750c5a9d9754abccView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000i-0900000000-7a5c54ced5b83f291e67View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0006-0900000000-e6b451ee354ed2717160View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-000i-9500000000-887e5157431b2908f31eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-0006-1900000000-06f7059894cc245cb344View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-0006-0900000000-89a88f44f08b8b68d5c1View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Brain
  • Epidermis
  • Fibroblasts
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Tryptophan MetabolismSMP00063map00380
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.023 +/- 0.010 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.03 +/- 0.007 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0040 +/- 0.00014 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.07 (0.06-0.08) uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0019 (0.0017-0.0021) uMAdult (>18 years old)FemaleNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.001 (0.0009-0.0011) uMAdult (>18 years old)MaleNormal details
UrineDetected and Quantified5.232 +/- 0.546 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified1.34 +/- 0.30 umol/mmol creatinineAdult (>18 years old)BothNormal
    • Geigy Scientific ...
    • West Cadwell, N.J...
    • Basel, Switzerlan...
details
UrineDetected and Quantified16.508 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified0.73-1.1 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified1.53 (0.66-4.13) umol/mmol creatinineAdult (>18 years old)Not SpecifiedNormal
    • Geigy Scientific ...
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified1.6 (0.8-4.2) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified0.62-0.86 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified2.6(0.9-4.1) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.80 +/- 0.40 uMAdult (>18 years old)Bothuremia details
BloodDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothColorectal cancer details
Cerebrospinal Fluid (CSF)Detected and Quantified0.06 (0.06-0.07) uMAdult (>18 years old)Not Specified
Malaria
details
Cerebrospinal Fluid (CSF)Detected and Quantified1.23 (0.18-8.40) uMNot SpecifiedNot Specified
Anemia
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.21 (0.2-0.3) uMNot SpecifiedNot Specified
Malaria
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.07 (0.0-34.1) uMNot SpecifiedNot Specified
Tuberculous meningitis
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.05 (0.02-0.10) uMNot SpecifiedNot Specified
Convulsions
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.05 (0.01-0.25) uMNot SpecifiedNot Specified
Malaria
details
UrineDetected and Quantified1.881 +/- 0.513 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified20.976 +/- 3.813 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified117.043 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Gastroesophageal reflux disease
    • Mordechai, Hien, ...
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothColorectal cancer details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Colorectal cancer
details
Associated Disorders and Diseases
Disease References
Anemia
  1. 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. [12964115 ]
Convulsion
  1. 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. [12964115 ]
Malaria
  1. 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. [11865422 ]
  2. 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. [12964115 ]
Tuberculous meningitis
  1. 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. [12964115 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022200
KNApSAcK IDNot Available
Chemspider ID3712
KEGG Compound IDC01717
BioCyc IDNot Available
BiGG ID38234
Wikipedia LinkKynurenic acid
NuGOwiki LinkHMDB00715
Metagene LinkHMDB00715
METLIN ID5683
PubChem Compound3845
PDB IDKYA
ChEBI ID18344
References
Synthesis ReferenceStone, T. W. Development and therapeutic potential of kynurenic acid and kynurenine derivatives for neuroprotection. Trends in Pharmacological Sciences (2000), 21(4), 149-154.
Material Safety Data Sheet (MSDS)Download (PDF)
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. [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. [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. [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. [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. [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. [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. [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. [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. [16434056 ]
  10. Milart P, Sikorski R: [Kynurenic acid concentration in blood and urine during normal pregnancy] Ginekol Pol. 1998 Dec;69(12):968-73. [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. [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. [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. [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. [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. [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. [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. [16088227 ]
  18. Muller N, Schwarz M: Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission. Neurotox Res. 2006 Oct;10(2):131-48. [17062375 ]

Enzymes

General function:
Involved in 1-aminocyclopropane-1-carboxylate synthase activity
Specific function:
Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). Metabolizes the cysteine conjugates of certain halogenated alkenes and alkanes to form reactive metabolites. Catalyzes the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of the C-S or C-Se bond.
Gene Name:
CCBL1
Uniprot ID:
Q16773
Molecular weight:
47874.765
General function:
Involved in transferase activity, transferring nitrogenous groups
Specific function:
Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). May catalyze the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of the C-S or C-Se bond (By similarity). Has transaminase activity towards L-kynurenine, tryptophan, phenylalanine, serine, cysteine, methionine, histidine, glutamine and asparagine with glyoxylate as an amino group acceptor (in vitro). Has lower activity with 2-oxoglutarate as amino group acceptor (in vitro) (By similarity).
Gene Name:
CCBL2
Uniprot ID:
Q6YP21
Molecular weight:
51399.855