Kynurenine
l-Kynurenine is a metabolite of the amino acid l-tryptophan used in the production of niacin.
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IUPAC name
(S)-2-Amino-4-(2-aminophenyl)-4-oxo-butanoic acid | |
Other names
(S)-Kynurenine | |
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DrugBank | |
MeSH | Kynurenine |
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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). | |
Infobox references | |
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]
Kynurenine pathway dysfunction
Dysfunctional states of distinct steps of the kynurenine pathway (e.g. kynurenine, kynurenic acid, quinolinic acid, anthranilic acid, 3-Hydroxykynurenine) have been described for a number of disorders, e.g.:[14]
- HIV dementia
- Tourette syndrome
- Tic disorders
- Psychiatric disorders (e.g. Schizophrenia, major depression, anxiety disorders)
- Multiple sclerosis
- Huntington's disease
- Encephalopathies
- Lipid metabolism
- Liver fat metabolism
- Systemic lupus erythematosus
- Glutaric aciduria
- Vitamin B6 deficiency
- Eosinophilia-myalgia syndrome
Downregulation of kynurenine-3-monooxygenase (KMO) can be caused by genetic polymorphisms, cytokines, or both.[15][16] KMO deficiency leads to an accumulation of kynurenine and to a shift within the tryptophan metabolic pathway towards kynurenine acid and anthranilic acid.[17] Kynurenine-3-monooxygenase deficiency is associated with disorders of the brain (e.g. schizophrenia, tic disorders) and of the liver.[10][18][19][20][21]
See also
References
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- 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.
- Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, Miller AH (2003). "Interferon-alpha–induced changes in tryptophan metabolism". Biological Psychiatry. 54 (9): 906–14. doi:10.1016/S0006-3223(03)00173-2. PMID 14573318.
- 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.
- Guillemin GJ, Brew BJ, Noonan CE, Takikawa O, Cullen KM (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.
- 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.
- Gulaj E, Pawlak K, Bien B, Pawlak D (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.
- Swardfager W, Herrmann N, Dowlati Y, Oh PI, Kiss A, Walker SE, Lanctôt KL (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.
- 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.
- 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.
- Kynureninase, European Bioinformatics Institute
- Saito Y, Hayaishi O, Rothberg S (1957-12-01). "Studies on Oxygenases". The Journal of Biological Chemistry. 229 (2): 921–34. PMID 13502353.
- Stone TW (2001). "Kynurenines in the CNS: from endogenous obscurity to therapeutic importance". Progress in Neurobiology. 64 (2): 185–218. doi:10.1016/s0301-0082(00)00032-0. PMID 11240212.
- "Neurobiochemie" (in German).
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- 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.
- Holtze M, Saetre P, Engberg G, Schwieler L, Werge T, Andreassen OA, Hall H, Terenius L, Agartz I, Jönsson EG, Schalling M, Erhardt S (2012). "Kynurenine 3-monooxygenase polymorphisms: relevance for kynurenic acid synthesis in patients with schizophrenia and healthy controls". J Psychiatry Neurosci. 37 (1): 53–7. doi:10.1503/jpn.100175. PMC 3244499. PMID 21693093.
- Campbell BM, Charych E, Lee AW, Möller T (2014). "Kynurenines in CNS disease: regulation by inflammatory cytokines". Front Neurosci. 8: 12. doi:10.3389/fnins.2014.00012. PMC 3915289. PMID 24567701.
- Buness A, Roth A, Herrmann A, Schmitz O, Kamp H, Busch K, Suter L (2014). "Identification of metabolites, clinical chemistry markers and transcripts associated with hepatotoxicity". PLoS ONE. 9 (5): e97249. Bibcode:2014PLoSO...997249B. doi:10.1371/journal.pone.0097249. PMC 4023975. PMID 24836604.
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