Kynurenine

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Kynurenine
L-Kynurenine.svg
Identifiers
CAS number 343-65-7 N, (D/L)
2922-83-0 (L)
13441-51-5 (D)
PubChem 846
ChemSpider 141580 YesY
DrugBank DB02070
MeSH Kynurenine
ChEBI CHEBI:57959 YesY
ChEMBL CHEMBL498416 YesY
Jmol-3D images Image 1
Properties
Molecular formula C10H12N2O3
Molar mass 208.21 g mol−1
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references

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] Kynurenine production is increased in Alzheimer's disease[6] and cardiovascular disease[7] where its metabolites are associated with cognitive deficits[8] and depressive symptoms.[9] Kynurenine is also associated with tics.[10][11]

Kynureninase catabolizes the conversion of kynurenine into anthranilic acid[12] while kynurenine-oxoglutarate transaminase catabolizes its conversion into kynurenic acid. Kynurenine 3-hydroxylase converts kynurenine to 3-hydroxykynurenine.[13]

See also[edit]

References[edit]

  1. ^ a b Opitz, Christiane A.; Litzenburger, Ulrike M.; Sahm, Felix; Ott, Martina; Tritschler, Isabel; Trump, Saskia; Schumacher, Theresa; Jestaedt, Leonie et al. (2011). "An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor". Nature 478 (7368): 197–203. doi:10.1038/nature10491. PMID 21976023. 
  2. ^ Wang, Yutang; Liu, Hanzhong; McKenzie, Gavin; Witting, Paul K; Stasch, Johannes-Peter; Hahn, Michael; Changsirivathanathamrong, Dechaboon; Wu, Ben J et al. (2010). "Kynurenine is an endothelium-derived relaxing factor produced during inflammation". Nature Medicine 16 (3): 279–85. doi:10.1038/nm.2092. PMC 3556275. PMID 20190767. 
  3. ^ Nguyen, N. T.; 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. doi:10.1073/pnas.1014465107. 
  4. ^ Capuron, Lucile; Neurauter, Gabriele; Musselman, Dominique L; Lawson, David H; Nemeroff, Charles B; Fuchs, Dietmar; Miller, Andrew H (2003). "Interferon-alpha–induced changes in tryptophan metabolism". Biological Psychiatry 54 (9): 906–14. doi:10.1016/S0006-3223(03)00173-2. PMID 14573318. 
  5. ^ Wonodi, Ikwunga; 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. 
  6. ^ Guillemin, G. J.; Brew, B. J.; Noonan, C. E.; Takikawa, O.; Cullen, K. M. (2005). "Indoleamine 2,3 dioxygenase and quinolinic acid Immunoreactivity in Alzheimer's disease hippocampus". Neuropathology and Applied Neurobiology 31 (4): 395–404. doi:10.1111/j.1365-2990.2005.00655.x. PMID 16008823. 
  7. ^ Wirleitner, B.; Rudzite, V.; Neurauter, G.; Murr, C.; Kalnins, U.; Erglis, A.; Trusinskis, K.; Fuchs, D. (2003). "Immune activation and degradation of tryptophan in coronary heart disease". European Journal of Clinical Investigation 33 (7): 550–4. doi:10.1046/j.1365-2362.2003.01186.x. PMID 12814390. 
  8. ^ Pawlak, D; Bien, B; Pawlak, K; Gulaj, E (2010). "Kynurenine and its metabolites in Alzheimer's disease patients". Advances in Medical Sciences 55 (2): 204–11. doi:10.2478/v10039-010-0023-6. PMID 20639188. 
  9. ^ Swardfager, Walter; Herrmann, Nathan; Dowlati, Yekta; Oh, Paul I.; Kiss, Alexander; Walker, Scott E.; Lanctôt, Krista L. (2009). "Indoleamine 2,3-dioxygenase activation and depressive symptoms in patients with coronary artery disease". Psychoneuroendocrinology 34 (10): 1560–6. doi:10.1016/j.psyneuen.2009.05.019. PMID 19540675. 
  10. ^ Hoekstra, Pieter J.; Anderson, George M.; Troost, Pieter W.; Kallenberg, Cees G. M.; Minderaa, Ruud B. (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. 
  11. ^ McCreary, Andrew C.; Handley, Sheila L. (1995). "Kynurenine potentiates the DOI head shake in mice". Journal of Psychopharmacology 9 (1): 69–70. doi:10.1177/026988119500900112. PMID 22298697. 
  12. ^ Kynureninase, European Bioinformatics Institute
  13. ^ Saito, Yoshitaka; Hayaishi, Osamu; Rothberg, Simon (1957-12-01). "Studies on Oxygenases". The Journal of Biological Chemistry 229 (2): 921–34. PMID 13502353.