Tryptofaan is een essentieel aminozuur dat van belang is bij de opbouw van eiwit. Daarnaast wordt tryptofaan aangewend voor de biosynthese van de neurotransmitter serotonine en het ’slaapverwekkende hormoon’ melatonine. Minder bekend is de kynurenine-pathway, de belangrijkste afbraakroute van tryptofaan die o.a. leidt tot de aanmaak van nicotinezuur, een vorm van vitamine B3 (niacine),en de aanmaak andere tussenproducten die kynurenines worden genoemd. De kynurenine-pathway is een uitgebalanceerd systeem. Verdeling van enzymen en tussenproducten over verschillende celtypen zorgt ervoor dat specifieke regulatie mogelijk is. Verstoringen van de evenwichten binnen de pathway kan leiden tot ziekte. Volgens de laatste inzichten speelt de kynurenine-pathway een rol bij neurologische aandoeningen maar ook bij tumorproliferatie, ontstekingsprocessen, depressies en regulatie van de afweerrespons. Ook zijn er sterke aanwijzingen dat de kynurenine-pathway, al dan niet via ontstekingsreacties, een rol vervult bij het ontstaan van aderverkalking en hart- en vaatziekten.
Beste bezoeker, u heeft geen toegang.
Enkel (web)abonnees hebben toegang tot tijdschriftartikelen. Het webabonnement is nog in de maak.
U kunt zich wel alvast (gratis) registreren en tal van andere webartikelen raadplegen!
Auteur
Figuren
Verschenen in
Referenties
Bohar Z, Toldi J, Fulop F, Vecsei L. Changing the face of kynurenines and neurotoxicity: therapeutic considerations. Int J Mol Sci 2015; 16: 9772-9793.
Muller AJ, DuHadaway JB, Chang MY, Ramalingam A, Sutanto-Ward E, Boulden J, Soler AP, Mandik-Nayak L, Gilmour SK, Prendergast GC. Non-hematopoietic expression of IDO is integrally required for inflammatory tumor promotion. Cancer Immunol Immunother. 2010 Nov;59(11):1655-63
Silk JD, Lakhal S, Laynes R, Vallius L, Karydis I, Marcea C, Boyd CA, Cerundolo V. IDO induces expression of a novel tryptophan transporter in mouse and human tumor cells. J Immunol. 2011 Aug 15;187(4):1617-25
Clarke G, McKernan DP, Gaszner G, Quigley EM, Cryan JF, Dinan TG. A Distinct Profile of Tryptophan Metabolism along the Kynurenine Pathway Downstream of Toll-Like Receptor Activation in Irritable Bowel Syndrome. Front Pharmacol. 2012 May 21;3:90. doi: 10.3389/fphar.2012.00090. PubMed PMID: 22661947; PubMed Central PMCID: PMC3357104.
ALS
Lee JM, Tan V, Lovejoy D, Braidy N, Rowe DB, Brew BJ, Guillemin GJ. Involvement of quinolinic acid in the neuropathogenesis of amyotrophic lateral sclerosis. Neuropharmacology. 2017 Jan;112(Pt B):346-364. doi:
10.1016/j.neuropharm.2016.05.011. Review. PubMed PMID: 27265569.
Alzheimer
Widner, B.; Leblhuber, F.; Walli, J.; Tilz, G.P.; Demel, U.; Fuchs, D. Tryptophan degradation and immune activation in Alzheimer’s disease. J. Neural Transm. 2000, 107, 343–353.
Schwarz, M.J.; Guillemin, G.J.; Teipel, S.J.; Buerger, K.; Hampel, H. Increased 3-hydroxykynurenine serum concentrations differentiate Alzheimer’s disease patients from controls. Eur. Arch. Psychiatry Clin. Neurosci. 2013, 263, 345–352.
Guillemin GJ, Brew BJ, Noonan CE, Takikawa O, Cullen KM (2005). Indoleamine 2,3 dioxygenase and quinolinic acid immunoreactivity in Alzheimer’s disease hippocampus. Neuropathol Appl Neurobiol 31: 395–404.
Yamada A, Akimoto H, Kagawa S, Guillemin GJ, Takikawa O (2009). Proinflammatory cytokine interferon-gamma increases induction of indoleamine 2,3-dioxygenase in monocytic cells
primed with amyloid beta peptide 1-42: implications for the pathogenesis of Alzheimer’s disease. J Neurochem 110: 791–800.
Walker DG, Link J, Lue L-F, Dalsing-Hernandez JE, Boyes BE (2006). Gene expression changes by amyloid beta peptide-stimulated BJP T W Stone and L G Darlington 1226 British Journal of Pharmacology (2013) 169 1211–1227
Parkinson
Ogawa T, Matson WR, Beal MF, et al. Kynurenine pathway abnormalities in Parkinson's disease. Neurology 1992; 42: 1702-1706
Lewitt PA, Li J, Lu M, et al. 3-hydroxykynurenine and other Parkinson's disease biomarkers discovered by metabolomic analysis. Mov Disord 2013; 28: 1653-1660
Németh H, Toldi J, Vécsei L. Kynurenines, Parkinson's disease and other neurodegenerative disorders: preclinical and clinical studies. J Neural Transm Suppl. 2006;(70):285-304. Review. PubMed PMID: 17017544.
Lin, M.T.; Beal, M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006, 443, 787–795. Int. J. Mol. Sci. 2015, 16 9790
Zadori, D.; Szalardy, L.; Toldi, J.; Fulop, F.; Klivenyi, P.; Vecsei, L. Some molecular mechanisms of dopaminergic and glutamatergic dysfunctioning in Parkinson’s disease. J. Neural Transm. 2013, 120, 673–681
Widner, B.; Leblhuber, F.; Fuchs, D. Increased neopterin production and tryptophan degradation in advanced Parkinson’s disease. J. Neural Transm. 2002, 109, 181–189.
Ogawa, T.; Matson, W.R.; Beal, M.F.; Myers, R.H.; Bird, E.D.; Milbury, P.; Saso, S. Kynurenine pathway abnormalities in Parkinson’s disease. Neurology 1992, 42, 1702–1706
Lewitt, P.A.; Li, J.; Lu, M.; Beach, T.G.; Adler, C.H.; Guo, L. 3-hydroxykynurenine and other Parkinson’s disease biomarkers discovered by metabolomic analysis. Mov. Disord. 2013, 28, 1653–1660
Huntington
Heyes, M.P.; Swartz, K.J.; Markey, S.P.; Beal, M.F. Regional brain and cerebrospinal fluid quinolinic acid concentrations in Huntington’s disease. Neurosci. Lett. 1991, 122, 265–269.
Beal, M.F.; Matson, W.R.; Storey, E.; Milbury, P.; Ryan, E.A.; Ogawa, T.; Bird, E.D. Kynurenic acid concentrations are reduced in Huntington’s disease cerebral cortex. J. Neurol. Sci. 1992, 108, 80–87.
Beal, M.F.; Matson, W.R.; Swartz, K.J.; Gamache, P.H.; Bird, E.D. Kynurenine pathway measurements in Huntington’s disease striatum: Evidence for reduced formation of kynurenic acid. J. Neurochem. 1990, 55, 1327–1339.
Heyes, M.P.; Saito, K.; Crowley, J.S.; Davis, L.E.; Demitrack, M.A.; Der, M.; Dilling, L.A.; Elia, J.; Kruesi, M.J.; Lackner, A.; et al. Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain 1992, 115 Pt 5, 1249–1273.
Jauch, D.; Urbanska, E.M.; Guidetti, P.; Bird, E.D.; Vonsattel, J.P.; Whetsell, W.O., Jr.; Schwarcz, R. Dysfunction of brain kynurenic acid metabolism in Huntington’s disease: Focus on kynurenine aminotransferases. J. Neurol. Sci. 1995, 130, 39–47.
Pearson, S.J.; Reynolds, G.P. Increased brain concentrations of a neurotoxin, 3-hydroxykynurenine,
in Huntington’s disease. Neurosci. Lett. 1992, 144, 199–201.
Guidetti, P.; Luthi-Carter, R.E.; Augood, S.J.; Schwarcz, R. Neostriatal and cortical quinolinate
levels are increased in early grade Huntington’s disease. Neurobiol. Dis. 2004, 17, 455–461
MS
Monaco, F.; Fumero, S.; Mondino, A.; Mutani, R. Plasma and cerebrospinal fluid tryptophan
in multiple sclerosis and degenerative diseases. J. Neurol. Neurosurg. Psychiatry 1979, 42,
640–641.
Ott, M.; Demisch, L.; Engelhardt, W.; Fischer, P.A. Interleukin-2, soluble interleukin-2-receptor, neopterin, L-tryptophan and β2-microglobulin levels in CSF and serum of patients with relapsing-remitting or chronic-progressive multiple sclerosis. J. Neurol. 1993, 241, 108–114
Hartai, Z.; Klivenyi, P.; Janaky, T.; Penke, B.; Dux, L.; Vecsei, L. Kynurenine metabolism in multiple sclerosis. Acta Neurol. Scand. 2005, 112, 93–96.
Rejdak, K.; Bartosik-Psujek, H.; Dobosz, B.; Kocki, T.; Grieb, P.; Giovannoni, G.; Turski, W.A.; Stelmasiak, Z. Decreased level of kynurenic acid in cerebrospinal fluid of relapsing-onset multiple sclerosis patients. Neurosci. Lett. 2002, 331, 63–65
Rejdak, K.; Petzold, A.; Kocki, T.; Kurzepa, J.; Grieb, P.; Turski, W.A.; Stelmasiak, Z. Astrocytic activation in relation to inflammatory markers during clinical exacerbation of relapsing-remitting multiple sclerosis. J. Neural Transm. 2007, 114, 1011–1015
Amirkhani, A.; Rajda, C.; Arvidsson, B.; Bencsik, K.; Boda, K.; Seres, E.; Markides, K.E.; Vecsei, L.; Bergquist, J. Interferon-β affects the tryptophan metabolism in multiple sclerosis patients. Eur. J. Neurol. 2005, 12, 625–631.
Durastanti, V.; Lugaresi, A.; Bramanti, P.; Amato, M.; Bellantonio, P.; de Luca, G.; Picconi, O.; Fantozzi, R.; Locatelli, L.; Solda, A.; et al. Neopterin production and tryptophan degradation during 24-months therapy with interferon β-1a in multiple sclerosis patients. J. Transl. Med. 2011, 9, doi:10.1186/1479-5876-9-42.
HIV
Lee SA, Mefford JA, Huang Y, Witte JS, Martin JN, Haas DW, Mclaren PJ, Mushiroda T, Kubo M, Byakwaga H, Hunt PW, Kroetz DL. Host genetic predictors of the kynurenine pathway of tryptophan catabolism among treated HIV-infected Ugandans. AIDS. 2016 Jul 17;30(11):1807-15. doi: 10.1097/QAD.0000000000001124.
PubMed PMID: 27088321; PubMed Central PMCID: PMC4925250.
Routy JP, Mehraj V, Vyboh K, Cao W, Kema I, Jenabian MA. Clinical Relevance of Kynurenine Pathway in HIV/AIDS: An Immune Checkpoint at the Crossroads of Metabolism and Inflammation. AIDS Rev. 2015 Apr-Jun;17(2):96-106. Review. PubMed PMID: 26035167.
Tang AM, Graham NM, Saah AJ. Effects of micronutrient intake on survival in human immunodeficiency virus type 1 infection. Am J Epidemiol. 1996 Jun 15;143(12):1244-56. PubMed PMID: 8651223
