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Kynurenine metabolism in health and disease

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Abstract

Kynurenine is a small molecule derived from tryptophan when this amino acid is metabolised via the kynurenine pathway. The biological activity of kynurenine and its metabolites (kynurenines) is well recognised. Therefore, understanding the regulation of the subsequent biochemical reactions is essential for the design of therapeutic strategies which aim to interfere with the kynurenine pathway. However, kynurenine concentration in the body may not only be determined by the efficiency of kynurenine synthesis but also by the rate of kynurenine clearance. In this review, current knowledge about the mechanisms of kynurenine production and routes of its clearance is presented. In addition, the involvement of kynurenine and its metabolites in the biology of different T cell subsets (including Th17 cells and regulatory T cells) and neuronal cells is discussed.

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References

  • Allegri G, Costa CV, Bertazzo A, Biasiolo M, Ragazzi E (2003) Enzyme activities of tryptophan metabolism along the kynurenine pathway in various species of animals. Farmaco 58:829–836

    Article  PubMed  CAS  Google Scholar 

  • Amori L, Guidetti P, Pellicciari R, Kajii Y, Schwarcz R (2009) On the relationship between the two branches of the kynurenine pathway in the rat brain in vivo. J Neurochem 109:316–325

    Article  PubMed  CAS  Google Scholar 

  • Baban B, Chandler P, McCool D, Marshall B, Munn DH, Mellor AL (2004) Indoleamine 2,3-dioxygenase expression is restricted to fetal trophoblast giant cells during murine gestation and is maternal genome specific. J Reprod Immunol 61:67–77

    Article  PubMed  CAS  Google Scholar 

  • Barth MC, Ahluwalia N, Anderson TJ, Hardy GJ, Sinha S, Alvarez-Cardona JA, Pruitt IE, Rhee EP, Colvin RA, Gerszten RE (2009) Kynurenic acid triggers firm arrest of leukocytes to vascular endothelium under flow conditions. J Biol Chem 284:19189–19195

    Article  PubMed  CAS  Google Scholar 

  • Bauer TM, Jiga LP, Chuang JJ, Randazzo M, Opelz G, Terness P (2005) Studying the immunosuppressive role of indoleamine 2,3-dioxygenase: tryptophan metabolites suppress rat allogeneic T-cell responses in vitro and in vivo. Transplant Int 18:95–100

    Article  CAS  Google Scholar 

  • Beadle GW, Mitchell HK, Nyc JF (1947) Kynurenine as an intermediate in the formation of nicotinic acid from tryptophane by Neurospora. Proc Natl Acad Sci USA 33:155–158

    Article  PubMed  CAS  Google Scholar 

  • Belladonna ML, Grohmann U, Guidetti P, Volpi C, Bianchi R, Fioretti MC, Schwarcz R, Fallarino F, Puccetti P (2006) Kynurenine pathway enzymes in dendritic cells initiate tolerogenesis in the absence of functional IDO. J Immunol 177:130–137

    PubMed  CAS  Google Scholar 

  • Bertazzo A, Ragazzi E, Biasiolo M, Costa CV, Allegri G (2001) Enzyme activities involved in tryptophan metabolism along the kynurenine pathway in rabbits. Biochim Biophys Acta 1527:167–175

    PubMed  CAS  Google Scholar 

  • Black AR, Black JD, Azizkhan-Clifford J (2001) Sp1 and kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol 188:143–160

    Article  PubMed  CAS  Google Scholar 

  • Breton J, Avanzi N, Magagnin S, Covini N, Magistrelli G, Cozzi L, Isacchi A (2000) Functional characterization and mechanism of action of recombinant human kynurenine 3-hydroxylase. Eur J Biochem 267:1092–1099

    Article  PubMed  CAS  Google Scholar 

  • Carpenedo R, Chiarugi A, Russi P, Lombardi G, Carla V, Pellicciari R, Mattoli L, Moroni F (1994) Inhibitors of kynurenine hydroxylase and kynureninase increase cerebral formation of kynurenate and have sedative and anticonvulsant activities. Neuroscience 61:237–243

    Article  PubMed  CAS  Google Scholar 

  • Chiarugi A, Moroni F (1999) Quinolinic acid formation in immune-activated mice: studies with (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(-3-nitrophenyl)thiazol-2yl]-benzenesulfonamide (Ro 61–8048), two potent and selective inhibitors of kynurenine hydroxylase. Neuropharmacology 38:1225–1233

    Article  PubMed  CAS  Google Scholar 

  • Comai S, Costa CV, Ragazzi E, Bertazzo A, Allegri G (2005) The effect of age on the enzyme activities of tryptophan metabolism along the kynurenine pathway in rats. Clin Chim Acta 360:67–80

    Article  PubMed  CAS  Google Scholar 

  • Connor TJ, Starr N, O’Sullivan JB, Harkin A (2008) Induction of indolamine 2,3-dioxygenase and kynurenine 3-monooxygenase in rat brain following a systemic inflammatory challenge: a role for IFN-gamma? Neurosci Lett 441:29–34

    Article  PubMed  CAS  Google Scholar 

  • Cozzi A, Carpenedo R, Moroni F (1999) Kynurenine hydroxylase inhibitors reduce ischemic brain damage: studies with (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(nitrophenyl)thiazol-2yl]-benzenesulfonamide (Ro 61–8048) in models of focal or global brain ischemia. J Cereb Blood Flow Metab 19:771–777

    Article  PubMed  CAS  Google Scholar 

  • Criado G, Simelyte E, Inglis JJ, Essex D, Williams RO (2009) Indoleamine 2,3 dioxygenase-mediated tryptophan catabolism regulates accumulation of Th1/Th17 cells in the joint in collagen-induced arthritis. Arthritis Rheum 60:1342–1351

    Article  PubMed  Google Scholar 

  • del Amo EM, Urtti A, Yliperttula M (2008) Pharmacokinetic role of l-type amino acid transporters LAT1 and LAT2. Eur J Pharm Sci 35:161–174

    Article  PubMed  CAS  Google Scholar 

  • Desvignes L, Ernst JD (2009) Interferon-gamma-responsive nonhematopoietic cells regulate the immune response to Mycobacterium tuberculosis. Immunity 31:974–985

    Article  PubMed  CAS  Google Scholar 

  • Dobrovolsky VN, Bucci T, Heflich RH, Desjardins J, Richardson FC (2003) Mice deficient for cytosolic thymidine kinase gene develop fatal kidney disease. Mol Genet Metab 78:1–10

    Article  PubMed  CAS  Google Scholar 

  • Dobrovolsky VN, Bowyer JF, Pabarcus MK, Heflich RH, Williams LD, Doerge DR, Arvidsson B, Bergquist J, Casida JE (2005) Effect of arylformamidase (kynurenine formamidase) gene inactivation in mice on enzymatic activity, kynurenine pathway metabolites and phenotype. Biochim Biophys Acta 1724:163–172

    PubMed  CAS  Google Scholar 

  • Espey MG, Moffett JR, Namboodiri MA (1995) Temporal and spatial changes of quinolinic acid immunoreactivity in the immune system of lipopolysaccharide-stimulated mice. J Leukoc Biol 57:199–206

    PubMed  CAS  Google Scholar 

  • Fallarino F, Grohmann U, Vacca C, Bianchi R, Orabona C, Spreca A, Fioretti MC, Puccetti P (2002) T cell apoptosis by tryptophan catabolism. Cell Death Differ 9:1069–1077

    Article  PubMed  CAS  Google Scholar 

  • Fallarino F, Grohmann U, You S, McGrath BC, Cavener DR, Vacca C, Orabona C, Bianchi R, Belladonna ML, Volpi C et al (2006) The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 176:6752–6761

    PubMed  CAS  Google Scholar 

  • Frumento G, Rotondo R, Tonetti M, Damonte G, Benatti U, Ferrara GB (2002) Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. J Exp Med 196:459–468

    Article  PubMed  CAS  Google Scholar 

  • Fujigaki S, Saito K, Takemura M, Fujii H, Wada H, Noma A, Seishima M (1998) Species differences in l-tryptophan-kynurenine pathway metabolism: quantification of anthranilic acid and its related enzymes. Arch Biochem Biophys 358:329–335

    Article  PubMed  CAS  Google Scholar 

  • Gal EM, Sherman AD (1978) Synthesis and metabolism of l-kynurenine in rat brain. J Neurochem 30:607–613

    Article  PubMed  CAS  Google Scholar 

  • Giorgini F, Guidetti P, Nguyen Q, Bennett SC, Muchowski PJ (2005) A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease. Nat Genet 37:526–531

    Article  PubMed  CAS  Google Scholar 

  • Guidetti P, Eastman CL, Schwarcz R (1995) Metabolism of [5–3H]kynurenine in the rat brain in vivo: evidence for the existence of a functional kynurenine pathway. J Neurochem 65:2621–2632

    Article  PubMed  CAS  Google Scholar 

  • Hankes LV, Henderson LM (1957) The metabolism of carboxyl-labeled 3-hydroxyanthranilic acid in the rat. J Biol Chem 225:349–354

    PubMed  CAS  Google Scholar 

  • Harrington L, Srikanth CV, Antony R, Rhee SJ, Mellor AL, Shi HN, Cherayil BJ (2008) Deficiency of indoleamine 2,3-dioxygenase enhances commensal-induced antibody responses and protects against Citrobacter rodentium-induced colitis. Infect Immun 76:3045–3053

    Article  PubMed  CAS  Google Scholar 

  • Hayashi T, Mo JH, Gong X, Rossetto C, Jang A, Beck L, Elliott GI, Kufareva I, Abagyan R, Broide DH et al (2007) 3-Hydroxyanthranilic acid inhibits PDK1 activation and suppresses experimental asthma by inducing T cell apoptosis. Proc Natl Acad Sci USA 104:18619–18624

    Article  PubMed  CAS  Google Scholar 

  • Heyes MP, Chen CY, Major EO, Saito K (1997) Different kynurenine pathway enzymes limit quinolinic acid formation by various human cell types. Biochem J 326(Pt 2):351–356

    PubMed  CAS  Google Scholar 

  • Huang YW, Jansen RA, Fabbri E, Potter D, Liyanarachchi S, Chan MW, Liu JC, Crijns AP, Brown R, Nephew KP et al (2009) Identification of candidate epigenetic biomarkers for ovarian cancer detection. Oncol Rep 22:853–861

    Article  PubMed  CAS  Google Scholar 

  • Huang YW, Luo J, Weng YI, Mutch DG, Goodfellow PJ, Miller DS, Huang TH (2010) Promoter hypermethylation of CIDEA, HAAO and RXFP3 associated with microsatellite instability in endometrial carcinomas. Gynecol Oncol 117:239–247

    Article  PubMed  CAS  Google Scholar 

  • Inglis JJ, Criado G, Andrews M, Feldmann M, Williams RO, Selley ML (2007) The anti-allergic drug, N-(3′,4′-dimethoxycinnamonyl) anthranilic acid, exhibits potent anti-inflammatory and analgesic properties in arthritis. Rheumatology (Oxford) 46:1428–1432

    Article  CAS  Google Scholar 

  • Iwagaki H, Hizuta A, Tanaka N, Orita K (1995) Decreased serum tryptophan in patients with cancer cachexia correlates with increased serum neopterin. Immunol Invest 24:467–478

    Article  PubMed  CAS  Google Scholar 

  • Jakoby WB (1954) Kynurenine formamidase from Neurospora. J Biol Chem 207:657–663

    PubMed  CAS  Google Scholar 

  • Kanai M, Funakoshi H, Takahashi H, Hayakawa T, Mizuno S, Matsumoto K, Nakamura T (2009) Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice. Mol Brain 2:8

    Article  PubMed  Google Scholar 

  • Kaper T, Looger LL, Takanaga H, Platten M, Steinman L, Frommer WB (2007) Nanosensor detection of an immunoregulatory tryptophan influx/kynurenine efflux cycle. PLoS Biol 5:e257

    Article  PubMed  Google Scholar 

  • Kincses ZT, Toldi J, Vecsei L (2010) Kynurenines, neurodegeneration and Alzheimer’s disease. J Cell Mol Med 14(8):2045–2054

    Article  PubMed  CAS  Google Scholar 

  • Leblhuber F, Walli J, Jellinger K, Tilz GP, Widner B, Laccone F, Fuchs D (1998) Activated immune system in patients with Huntington’s disease. Clin Chem Lab Med 36:747–750

    Article  PubMed  CAS  Google Scholar 

  • Lee SM, Lee YS, Choi JH, Park SG, Choi IW, Joo YD, Lee WS, Lee JN, Choi I, Seo SK (2010) Tryptophan metabolite 3-hydroxyanthranilic acid selectively induces activated T cell death via intracellular GSH depletion. Immunol Lett 132:53–60

    Article  PubMed  CAS  Google Scholar 

  • Luthman J (2000) Anticonvulsant effects of the 3-hydroxyanthranilic acid dioxygenase inhibitor NCR-631. Amino Acids 19:325–334

    Article  PubMed  CAS  Google Scholar 

  • Luthman J, Radesater AC, Oberg C (1998) Effects of the 3-hydroxyanthranilic acid analogue NCR-631 on anoxia-, IL-1 beta- and LPS-induced hippocampal pyramidal cell loss in vitro. Amino Acids 14:263–269

    Article  PubMed  CAS  Google Scholar 

  • McIlroy D, Tanguy-Royer S, Le Meur N, Guisle I, Royer PJ, Leger J, Meflah K, Gregoire M (2005) Profiling dendritic cell maturation with dedicated microarrays. J Leukoc Biol 78:794–803

    Article  PubMed  CAS  Google Scholar 

  • Mehler AH, Knox WE (1950) The conversion of tryptophan to kynurenine in liver II. The enzymatic hydrolysis of formylkynurenine. J Biol Chem 187:431–438

    PubMed  CAS  Google Scholar 

  • Moffett JR, Namboodiri MA (2003) Tryptophan and the immune response. Immunol Cell Biol 81:247–265

    Article  PubMed  CAS  Google Scholar 

  • Moffett JR, Blinder KL, Venkateshan CN, Namboodiri MA (1998) Differential effects of kynurenine and tryptophan treatment on quinolinate immunoreactivity in rat lymphoid and non-lymphoid organs. Cell Tissue Res 293:525–534

    Article  PubMed  CAS  Google Scholar 

  • Morita T, Saito K, Takemura M, Maekawa N, Fujigaki S, Fujii H, Wada H, Takeuchi S, Noma A, Seishima M (2001) 3-Hydroxyanthranilic acid, an l-tryptophan metabolite, induces apoptosis in monocyte-derived cells stimulated by interferon-gamma. Ann Clin Biochem 38:242–251

    Article  PubMed  CAS  Google Scholar 

  • Munn DH, Sharma MD, Baban B, Harding HP, Zhang Y, Ron D, Mellor AL (2005) GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity 22:633–642

    Article  PubMed  CAS  Google Scholar 

  • Nemeth H, Toldi J, Vecsei L (2005) Role of kynurenines in the central and peripheral nervous systems. Curr Neurovasc Res 2:249–260

    Article  PubMed  Google Scholar 

  • Nishimoto Y, Takeuchi F, Shibata Y (1979) Purification of l-kynurenine 3-hydroxylase by affinity chromatography. J Chromatogr 169:357–364

    Article  PubMed  CAS  Google Scholar 

  • O’Connor JC, Lawson MA, Andre C, Briley EM, Szegedi SS, Lestage J, Castanon N, Herkenham M, Dantzer R, Kelley KW (2009) Induction of IDO by bacille Calmette-Guerin is responsible for development of murine depressive-like behavior. J Immunol 182:3202–3212

    Article  PubMed  Google Scholar 

  • Okuda S, Nishiyama N, Saito H, Katsuki H (1996) Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine. Proc Natl Acad Sci USA 93:12553–12558

    Article  PubMed  CAS  Google Scholar 

  • Okuda S, Nishiyama N, Saito H, Katsuki H (1998) 3-Hydroxykynurenine, an endogenous oxidative stress generator, causes neuronal cell death with apoptotic features and region selectivity. J Neurochem 70:299–307

    Article  PubMed  CAS  Google Scholar 

  • Oxenkrug GF (2007) Genetic and hormonal regulation of tryptophan kynurenine metabolism: implications for vascular cognitive impairment, major depressive disorder, and aging. Ann NY Acad Sci 1122:35–49

    Article  PubMed  CAS  Google Scholar 

  • Pellegrin K, Neurauter G, Wirleitner B, Fleming AW, Peterson VM, Fuchs D (2005) Enhanced enzymatic degradation of tryptophan by indoleamine 2,3-dioxygenase contributes to the tryptophan-deficient state seen after major trauma. Shock 23:209–215

    PubMed  CAS  Google Scholar 

  • Platten M, Ho PP, Youssef S, Fontoura P, Garren H, Hur EM, Gupta R, Lee LY, Kidd BA, Robinson WH et al (2005) Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science 310:850–855

    Article  PubMed  CAS  Google Scholar 

  • Ploder M, Spittler A, Schroecksnadel K, Neurauter G, Pelinka LE, Roth E, Fuchs D (2009) Tryptophan degradation in multiple trauma patients: survivors compared with non-survivors. Clin Sci (Lond) 116:593–598

    Article  CAS  Google Scholar 

  • Prendergast GC (2008) Immune escape as a fundamental trait of cancer: focus on IDO. Oncogene 27:3889–3900

    Article  PubMed  CAS  Google Scholar 

  • Qiu H, Garcia-Barrio MT, Hinnebusch AG (1998) Dimerization by translation initiation factor 2 kinase GCN2 is mediated by interactions in the C-terminal ribosome-binding region and the protein kinase domain. Mol Cell Biol 18:2697–2711

    PubMed  CAS  Google Scholar 

  • Robinson CM, Hale PT, Carlin JM (2005) The role of IFN-gamma and TNF-alpha-responsive regulatory elements in the synergistic induction of indoleamine dioxygenase. J Interferon Cytokine Res 25:20–30

    Article  PubMed  CAS  Google Scholar 

  • Russo S, Kema IP, Fokkema MR, Boon JC, Willemse PH, de Vries EG, den Boer JA, Korf J (2003) Tryptophan as a link between psychopathology and somatic states. Psychosom Med 65:665–671

    Article  PubMed  CAS  Google Scholar 

  • Saito K, Crowley JS, Markey SP, Heyes MP (1993) A mechanism for increased quinolinic acid formation following acute systemic immune stimulation. J Biol Chem 268:15496–15503

    PubMed  CAS  Google Scholar 

  • Salter M, Knowles RG, Pogson CI (1986) Quantification of the importance of individual steps in the control of aromatic amino acid metabolism. Biochem J 234:635–647

    PubMed  CAS  Google Scholar 

  • Sapko MT, Guidetti P, Yu P, Tagle DA, Pellicciari R, Schwarcz R (2006) Endogenous kynurenate controls the vulnerability of striatal neurons to quinolinate: implications for Huntington’s disease. Exp Neurol 197:31–40

    Article  PubMed  CAS  Google Scholar 

  • Schroecksnadel K, Kaser S, Ledochowski M, Neurauter G, Mur E, Herold M, Fuchs D (2003) Increased degradation of tryptophan in blood of patients with rheumatoid arthritis. J Rheumatol 30:1935–1939

    PubMed  CAS  Google Scholar 

  • Schuettengruber B, Doetzlhofer A, Kroboth K, Wintersberger E, Seiser C (2003) Alternate activation of two divergently transcribed mouse genes from a bidirectional promoter is linked to changes in histone modification. J Biol Chem 278:1784–1793

    Article  PubMed  CAS  Google Scholar 

  • Schwarcz R, Pellicciari R (2002) Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities. J Pharmacol Exp Ther 303:1–10

    Article  PubMed  CAS  Google Scholar 

  • Speciale C, Hares K, Schwarcz R, Brookes N (1989) High-affinity uptake of l-kynurenine by a Na+-independent transporter of neutral amino acids in astrocytes. J Neurosci 9:2066–2072

    PubMed  CAS  Google Scholar 

  • Stone TW, Darlington LG (2002) Endogenous kynurenines as targets for drug discovery and development. Nat Rev Drug Discov 1:609–620

    Article  PubMed  CAS  Google Scholar 

  • Stone TW, Behan WM, Jones PA, Darlington LG, Smith RA (2001) The role of kynurenines in the production of neuronal death, and the neuroprotective effect of purines. J Alzheimers Dis 3:355–366

    PubMed  CAS  Google Scholar 

  • Taher YA, Piavaux BJ, Gras R, van Esch BC, Hofman GA, Bloksma N, Henricks PA, van Oosterhout AJ (2008) Indoleamine 2,3-dioxygenase-dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model. J Allergy Clin Immunol 121:983–991 e982

    Google Scholar 

  • Takeuchi F, Shibata Y (1984) Kynurenine metabolism in vitamin-B-6-deficient rat liver after tryptophan injection. Biochem J 220:693–699

    PubMed  CAS  Google Scholar 

  • Takikawa O, Yoshida R, Kido R, Hayaishi O (1986) Tryptophan degradation in mice initiated by indoleamine 2,3-dioxygenase. J Biol Chem 261:3648–3653

    PubMed  CAS  Google Scholar 

  • Tanizawa K, Soda K (1979a) Inducible and constitutive kynureninases. Control of the inducible enzyme activity by transamination and inhibition of the constitutive enzyme by 3-hydroxyanthranilate. J Biochem 86:499–508

    PubMed  CAS  Google Scholar 

  • Tanizawa K, Soda K (1979b) The mechanism of kynurenine hydrolysis catalyzed by kynureninase. J Biochem 86:1199–1209

    PubMed  CAS  Google Scholar 

  • Terness P, Bauer TM, Rose L, Dufter C, Watzlik A, Simon H, Opelz G (2002) Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J Exp Med 196:447–457

    Article  PubMed  CAS  Google Scholar 

  • Ueda T, Otsuka H, Goda K, Ishiguro I, Naito J, Kotake Y (1978) The metabolism of [carboxyl-14C]anthranilic acid. I. The incorporation of radioactivity into NAD+ and NADP+. J Biochem 84:687–696

    PubMed  CAS  Google Scholar 

  • von Bubnoff D, Matz H, Frahnert C, Rao ML, Hanau D, de la Salle H, Bieber T (2002) Fcepsilon RI induces the tryptophan degradation pathway involved in regulating T cell responses. J Immunol 169:1810–1816

    Google Scholar 

  • Wagner CA, Lang F, Broer S (2001) Function and structure of heterodimeric amino acid transporters. Am J Physiol Cell Physiol 281:C1077–C1093

    PubMed  CAS  Google Scholar 

  • Walsh JL, Todd WP, Carpenter BK, Schwarcz R (1991) 4-Halo-3-Hydroxyanthranilic acids: potent competitive inhibitors of 3-hydroxy-anthranilic acid oxygenase in vitro. Biochem Pharmacol 42:985–990

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Simonavicius N, Wu X, Swaminath G, Reagan J, Tian H, Ling L (2006) Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. J Biol Chem 281:22021–22028

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Liu H, McKenzie G, Witting PK, Stasch JP, Hahn M, Changsirivathanathamrong D, Wu BJ, Ball HJ, Thomas SR et al (2010) Kynurenine is an endothelium-derived relaxing factor produced during inflammation. Nat Med 16:279–285

    Article  PubMed  CAS  Google Scholar 

  • Wek RC, Jiang HY, Anthony TG (2006) Coping with stress: eIF2 kinases and translational control. Biochem Soc Trans 34:7–11

    Article  PubMed  CAS  Google Scholar 

  • Widner B, Sepp N, Kowald E, Ortner U, Wirleitner B, Fritsch P, Baier-Bitterlich G, Fuchs D (2000) Enhanced tryptophan degradation in systemic lupus erythematosus. Immunobiology 201:621–630

    PubMed  CAS  Google Scholar 

  • Widner B, Laich A, Sperner-Unterweger B, Ledochowski M, Fuchs D (2002) Neopterin production, tryptophan degradation, and mental depression—what is the link? Brain Behav Immun 16:590–595

    Article  PubMed  CAS  Google Scholar 

  • Yeh JK, Brown RR (1977) Effects of vitamin B-6 deficiency and tryptophan loading on urinary excretion of tryptophan metabolites in mammals. J Nutr 107:261–271

    PubMed  CAS  Google Scholar 

  • Zaborske JM, Narasimhan J, Jiang L, Wek SA, Dittmar KA, Freimoser F, Pan T, Wek RC (2009) Genome-wide analysis of tRNA charging and activation of the eIF2 kinase Gcn2p. J Biol Chem 284:25254–25267

    Article  PubMed  CAS  Google Scholar 

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Kolodziej, L.R., Paleolog, E.M. & Williams, R.O. Kynurenine metabolism in health and disease. Amino Acids 41, 1173–1183 (2011). https://doi.org/10.1007/s00726-010-0787-9

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