l-Kynurenine
Skeletal formula of L-kynurenine
Ball-and-stick model of the L-kynurenine molecule as a zwitterion
Names
Preferred IUPAC name
(2S)-2-Amino-4-(2-aminophenyl)-4-oxo-butanoic acid
Other names
(S)-Kynurenine
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
MeSH Kynurenine
UNII
  • InChI=1S/C10H12N2O3/c11-7-4-2-1-3-6(7)9(13)5-8(12)10(14)15/h1-4,8H,5,11-12H2,(H,14,15)/t8-/m0/s1 checkY
    Key: YGPSJZOEDVAXAB-QMMMGPOBSA-N checkY
  • c1ccc(c(c1)C(=O)C[C@@H](C(=O)O)N)N
Properties
C10H12N2O3
Molar mass 208.217 g·mol−1
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 ?)

l-Kynurenine is a metabolite of the amino acid l-tryptophan used in the production of niacin.

Kynurenine is synthesized by the enzyme tryptophan dioxygenase, which is made primarily but not exclusively in the liver, and indoleamine 2,3-dioxygenase, which is made in many tissues in response to immune activation.[1] Kynurenine and its further breakdown products carry out diverse biological functions, including dilating blood vessels during inflammation[2] and regulating the immune response.[3] Some cancers increase kynurenine production, which increases tumor growth.[1]

Evidence suggests that increased kynurenine production may precipitate depressive symptoms associated with interferon treatment for hepatitis C.[4] Cognitive deficits in schizophrenia are associated with imbalances in the enzymes that break down kynurenine.[5] Blood levels of kynurenine are reduced in people with bipolar disorder.[6] Kynurenine production is increased in Alzheimer's disease[7] and cardiovascular disease[8] where its metabolites are associated with cognitive deficits[9] and depressive symptoms.[10] Kynurenine is also associated with tics.[11][12]

Kynureninase catabolizes the conversion of kynurenine into anthranilic acid[13] while kynurenine-oxoglutarate transaminase catabolizes its conversion into kynurenic acid. Kynurenine 3-hydroxylase converts kynurenine to 3-hydroxykynurenine.[14]

Kynurenine has also been identified as one of two compounds that makes up the pigment that gives the goldenrod crab spider its yellow color.[15]

The Kynurenine pathway, which connects quinolinic acid to tryptophan. The pathway is named for the first intermediate, kynurenine, which is a precursor to kynurenic acid and 3-hydroxykynurenine.[16]

Kynurenine pathway dysfunction

Dysfunctional states of distinct steps of the kynurenine pathway (such as kynurenine, kynurenic acid, quinolinic acid, anthranilic acid, 3-hydroxykynurenine) have been described for a number of disorders, including:[17]

Downregulation of kynurenine-3-monooxygenase (KMO) can be caused by genetic polymorphisms, cytokines, or both.[20][21] KMO deficiency leads to an accumulation of kynurenine and to a shift within the tryptophan metabolic pathway towards kynurenine acid and anthranilic acid.[22] Kynurenine-3-monooxygenase deficiency is associated with disorders of the brain (e.g. major depressive disorder, bipolar disorder, schizophrenia, tic disorders) [23] and of the liver.[11][24][25][26][27]

See also

References

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  3. ^ Nguyen NT, Kimura A, Nakahama T, Chinen I, Masuda K, Nohara K, Fujii-Kuriyama Y, Kishimoto T (2010). "Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism". Proceedings of the National Academy of Sciences. 107 (46): 19961–6. Bibcode:2010PNAS..10719961N. doi:10.1073/pnas.1014465107. PMC 2993339. PMID 21041655.
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  5. ^ Wonodi I, Stine OC, Sathyasaikumar KV, Roberts RC, Mitchell BD, Hong LE, Kajii Y, Thaker GK, Schwarcz R (2011). "Downregulated Kynurenine 3-Monooxygenase Gene Expression and Enzyme Activity in Schizophrenia and Genetic Association with Schizophrenia Endophenotypes". Archives of General Psychiatry. 68 (7): 665–74. doi:10.1001/archgenpsychiatry.2011.71. PMC 3855543. PMID 21727251.
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  11. ^ a b Hoekstra PJ, Anderson GM, Troost PW, Kallenberg CG, Minderaa RB (2007). "Plasma kynurenine and related measures in tic disorder patients". European Child & Adolescent Psychiatry. 16: 71–7. doi:10.1007/s00787-007-1009-1. PMID 17665285. S2CID 39150343.
  12. ^ McCreary AC, Handley SL (1995). "Kynurenine potentiates the DOI head shake in mice". Journal of Psychopharmacology. 9 (1): 69–70. doi:10.1177/026988119500900112. PMID 22298697. S2CID 28700510.
  13. ^ Kynureninase, European Bioinformatics Institute
  14. ^ Saito Y, Hayaishi O, Rothberg S (1957-12-01). "Studies on Oxygenases". The Journal of Biological Chemistry. 229 (2): 921–34. doi:10.1016/S0021-9258(19)63696-3. PMID 13502353.[permanent dead link]
  15. ^ Oxford, G. S.; Gillespie, R. G. (January 1998). "Evolution and Ecology of Spider Coloration". Annual Review of Entomology. 43 (1): 619–643. doi:10.1146/annurev.ento.43.1.619. ISSN 0066-4170. PMID 15012400. S2CID 6963733.
  16. ^ Schwarcz, Robert; John P. Bruno; Paul J. Muchowski; Hui-Qiu Wu (July 2012). "Kynurenines in the Mammalian Brain: When Physiology Meets Pathology". Nature Reviews Neuroscience. 13 (7): 465–477. doi:10.1038/nrn3257. PMC 3681811. PMID 22678511.
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  22. ^ Wonodi I, Stine OC, Sathyasaikumar KV, Roberts RC, Mitchell BD, Hong LE, Kajii Y, Thaker GK, Schwarcz R (2011). "Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes". Arch. Gen. Psychiatry. 68 (7): 665–74. doi:10.1001/archgenpsychiatry.2011.71. PMC 3855543. PMID 21727251.
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