- Tryptophan and the immune response
John R Moffett
Department of Anatomy, Uniformed Services University of the Health Sciences, Building C, Room 2109, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
Immunol Cell Biol 81:247-65. 2003
..mediate tolerance are not well understood, but recent findings have implicated tryptophan catabolism through the kynurenine metabolic pathway as one of many mechanisms involved...
- Kynurenine is an endothelium-derived relaxing factor produced during inflammation
Centre for Vascular Research, School of Medical Sciences Pathology and Bosch Institute, Faculty of Medicine, University of Sydney, Sydney, Australia
Nat Med 16:279-85. 2010
Control of blood vessel tone is central to vascular homeostasis. Here we show that metabolism of tryptophan to kynurenine by indoleamine 2,3-dioxygenase (Ido) expressed in endothelial cells contributes to arterial vessel relaxation and ..
- Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase
Immunogenetics Laboratory, National Cancer Research Institute, University of Genoa, Largo Rosanna Benzi 10, 16132 Genoa, Italy
J Exp Med 196:459-68. 2002
..The inhibitory role of tryptophan and of its catabolites was then tested. In the presence of tryptophan, only L-kynurenine and picolinic acid inhibit cell proliferation. In a tryptophan-free medium cell proliferation was not affected...
- Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites
Institute of Immunology, Department of Transplantation Immunology, University of Heidelberg, 69120 Heidelberg, Germany
J Exp Med 196:447-57. 2002
..Transgenic DCs decreased the concentration of tryptophan, increased the concentration of kynurenine, the main tryptophan metabolite, and suppressed allogeneic T cell proliferation in vitro...
- Inflammation-associated depression: from serotonin to kynurenine
Integrative Immunology and Behavior Program, Department of Animal Sciences, 227 Edward R Madigan Laboratory, 1201 West Gregory Drive, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
Psychoneuroendocrinology 36:426-36. 2011
..activation of the tryptophan degrading enzyme indoleamine 2,3-dioxygenase that generates potentially neurotoxic kynurenine metabolites such as 3-hydroxy kynurenine and quinolinic acid...
- Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
Nature 451:211-5. 2008
..Here we show that a superoxide-dependent step in tryptophan metabolism along the kynurenine pathway is blocked in CGD mice with lethal pulmonary aspergillosis, leading to unrestrained Vgamma1(+) ..
- Interleukin-1β: a new regulator of the kynurenine pathway affecting human hippocampal neurogenesis
Patricia A Zunszain
Section of Perinatal Psychiatry and Stress, Psychiatry and Immunology SPI Lab, Department of Psychological Medicine, Institute of Psychiatry, King s College London, London, UK
Neuropsychopharmacology 37:939-49. 2012
..Analysis of the enzymes that regulate the kynurenine pathway showed that IL-1β induced an upregulation of transcripts for indolamine-2,3-dioxygenase (IDO), ..
- Metabolic syndrome, age-associated neuroendocrine disorders, and dysregulation of tryptophan-kynurenine metabolism
Gregory F Oxenkrug
Department of Psychiatry, Tufts University Tufts Medical Center, Boston, Massachusetts 02111, USA
Ann N Y Acad Sci 1199:1-14. 2010
..is transcriptional induction of indoleamine 2,3-dioxygenase (IDO), rate-limiting enzyme of tryptophan (TRY)-kynurenine (KYN) pathway, by pro-inflammatory cytokines (PIC)...
- Kynurenine pathway enzymes in dendritic cells initiate tolerogenesis in the absence of functional IDO
Maria L Belladonna
Department of Experimental Medicine, University of Perugia, Via del Giochetto, Perugia 06126, Italy
J Immunol 177:130-7. 2006
..initiated by IDO, that are still unclear, including the role of enzymes that are downstream of IDO in the kynurenine pathway and the role of the associated production of kynurenines...
- IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity
M C Wichers
Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
Mol Psychiatry 10:538-44. 2005
..The enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan (TRP) into kynurenine (KYN) and which is stimulated by proinflammatory cytokines, may be implicated in the development of IFN-alpha-..
- 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
Department of Experimental Medicine, University of Perugia, Perugia, Italy
J Immunol 176:6752-61. 2006
- T cell apoptosis by tryptophan catabolism
Department of Experimental Medicine, University of Perugia, Italy
Cell Death Differ 9:1069-77. 2002
..We show here that tryptophan metabolites in the kynurenine pathway, such as 3-hydroxyanthranilic and quinolinic acids, will induce the selective apoptosis in vitro of ..
- An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells
Joshua D Mezrich
Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 7375, USA
J Immunol 185:3190-8. 2010
..In this paper, we demonstrate that kynurenine, the first breakdown product in the IDO-dependent tryptophan degradation pathway, activates the AHR...
- Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism
Nam Trung Nguyen
Laboratory of Immune Regulation, Osaka University World Premier International Immunology Frontier Research Center, Osaka 565 0871, Japan
Proc Natl Acad Sci U S A 107:19961-6. 2010
..indoleamine 2,3-dioxygenase (IDO) expression, an immunosuppressive enzyme that catabolizes tryptophan into kynurenine (Kyn) and other metabolites in DC...
- Tryptophan kynurenine metabolism as a common mediator of genetic and environmental impacts in major depressive disorder: the serotonin hypothesis revisited 40 years later
Gregory F Oxenkrug
Department of Psychiatry, Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts 02111, USA
Isr J Psychiatry Relat Sci 47:56-63. 2010
..corticosteroids levels, and metabolism of tryptophan is shunted away from serotonin production, and towards kynurenine production...
- IDO expression in the brain: a double-edged sword
Institute of Cell Biology and Neurobiology, Charite, Berlin, Germany
J Mol Med (Berl) 85:1351-9. 2007
..enzyme indoleamine-2,3-dioxygenase (IDO) initiates the first and rate-limiting step of the kynurenine pathway...
- Monitoring tryptophan metabolism in chronic immune activation
Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Fritz Pregl Strasse 3 A 6020 Innsbruck, Austria
Clin Chim Acta 364:82-90. 2006
..generation of neurotransmitter 5-hydroxytryptamine (serotonin) by tryptophan 5-hydroxylase, and the formation of kynurenine derivatives and nicotinamide adenine dinucleotides...
- Effect of systemic kynurenine on cortical spreading depression and its modulation by sex hormones in rat
Cephalic Pain Unit of GIGA Neurosciences, Liege University, CHU Sart Tilman, T4, 1, 4000 Liege, Belgium
Exp Neurol 236:207-14. 2012
..Kynurenic acid, a derivative of tryptophan metabolism, is an endogenous NMDA receptor antagonist whose cerebral concentrations can be augmented by systemic administration of its precursor L-kynurenine.
- The kynurenine system and immunoregulation
Department of Medical Microbiology and Immunobiology, University of Szeged, Dom ter 10, 6720, Szeged, Hungary
J Neural Transm 119:197-209. 2012
..A considerable amount of evidence has accumulated as concerns interactions between the kynurenine pathway, cytokines and the nervous system...
- Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, USA
J Pharmacol Exp Ther 303:1-10. 2002
Degradation of the essential amino acid tryptophan along the kynurenine pathway (KP) yields several neuroactive intermediates, including the free radical generator 3-hydroxykynurenine, the excitotoxic N-methyl-D-aspartate (NMDA) receptor ..
- Tryptophan/kynurenine metabolism in human leukocytes is independent of superoxide and is fully maintained in chronic granulomatous disease
Suk See De Ravin
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Blood 116:1755-60. 2010
..Based on recent mouse studies, the lack of O(2)(·)-dependent interferon γ (IFNγ)-induced synthesis of kynurenine (kyn), an anti-inflammatory tryptophan metabolite produced by indolamine 2,3 deoxygenase (IDO), was proposed as ..
- More rapid method for simultaneous measurement of tryptophan and kynurenine by HPLC
Institute for Medical Chemistry and Biochemistry, Leopold Franzens University, A 6020 Innsbruck, Austria
Clin Chem 48:579-81. 2002
- Serum tryptophan decrease correlates with immune activation and impaired quality of life in colorectal cancer
Department of Surgery, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK
Br J Cancer 86:1691-6. 2002
..Serum tryptophan, kynurenine, neopterin, interleukin 2 soluble receptor alpha (IL-2 sRalpha), soluble tumour necrosis factor receptor I (sTNF ..
- Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders
Department of Neurology, University of Szeged, POB 427, H 6701 Szeged, Hungary
J Neurol Sci 257:221-39. 2007
..Other pathogenetic factors are also briefly surveyed. The second part of the review deals with the kynurenine metabolic pathway, its alterations and their potential association with cellular energy impairment in certain ..
- Increased cortical kynurenate content in schizophrenia
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA
Biol Psychiatry 50:521-30. 2001
BACKGROUND: Metabolites of the kynurenine pathway of tryptophan degradation may play a role in the pathogenesis of several human brain diseases...
- L-Kynurenine, an amino acid identified as a sex pheromone in the urine of ovulated female masu salmon
Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo ku, Tokyo 113 8657, Japan
Proc Natl Acad Sci U S A 103:15370-4. 2006
..Bioassay-guided fractionation yielded an active compound that was identical to L-kynurenine in spectral and chromatographic properties. L-Kynurenine is a major metabolite of L-tryptophan in vertebrates...
- Reversal of the Kynurenine pathway of tryptophan catabolism may improve depression in ART-treated HIV-infected Ugandans
Norwegian Center for Addiction Research, University of Oslo, Oslo, Norway Alcohol Research Group, School of Public Health, University of California, Berkeley, CA Center for Global Health, Massachusetts General Hospital, Boston, MA Division of Global Psychiatry, Department of Psychiatry, Massachusetts General Hospital, Boston, MA Mbarara University of Science and Technology, Mbarara, Uganda University of California at San Francisco, San Francisco, CA Division of HIV AIDS, San Francisco General Hospital, University of California San Francisco, CA Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA Department of Global Health and Population, Harvard School of Public Health, Boston, MA and Ragon Institute of Massachusetts General Hospital, MIT and Harvard, Boston, MA
J Acquir Immune Defic Syndr 65:456-62. 2014
..We investigated the extent to which ART-mediated suppression of the kynurenine pathway of tryptophan catabolism (via indoleamine 2,3-dioxygenase-1 and potentially other sources) may correlate ..
- Systemic markers of interferon-γ-mediated immune activation and long-term prognosis in patients with stable coronary artery disease
Eva Ringdal Pedersen
Section for Cardiology, Institute of Medicine, University of Bergen, 5021 Bergen, Norway
Arterioscler Thromb Vasc Biol 31:698-704. 2011
..In activated macrophages, IFN-γ stimulates production of neopterin and conversion of tryptophan to kynurenine. We evaluated the relationships of plasma neopterin and plasma kynurenine:tryptophan ratio (KTR) to long-term ..
- Tryptophan catabolism via kynurenine production in Streptomyces coelicolor: identification of three genes coding for the enzymes of tryptophan to anthranilate pathway
F P Zummo
Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Universita degli Studi di Palermo, Viale delle Scienze Edificio 16, 90128 Palermo, Italy
Appl Microbiol Biotechnol 94:719-28. 2012
Most enzymes involved in tryptophan catabolism via kynurenine formation are highly conserved in Prokaryotes and Eukaryotes...
- Kynurenine pathway inhibition as a therapeutic strategy for neuroprotection
Trevor W Stone
Institute for Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
FEBS J 279:1386-97. 2012
The oxidative pathway for the metabolism of tryptophan along the kynurenine pathway generates quinolinic acid, an agonist at N-methyl-D-aspartate receptors, as well as kynurenic acid which is an antagonist at glutamate and nicotinic ..
- Excessive tryptophan catabolism along the kynurenine pathway precedes ongoing sepsis in critically ill patients
J P Zeden
Department of Immunology, Ernst Moritz Arndt University Greifswald, Greifswald, Germany
Anaesth Intensive Care 38:307-16. 2010
It has recently been shown that an increased plasma level of the tryptophan catabolite kynurenine is an early indicator for the development of sepsis in major trauma patients...
- NAD biosynthesis evolution in bacteria: lateral gene transfer of kynurenine pathway in Xanthomonadales and Flavobacteriales
Wanessa C Lima
Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Brazil
Mol Biol Evol 26:399-406. 2009
..by two distinct pathways, namely, the bacterial aspartate (aspartate-to-quinolinate) and the eukaryotic kynurenine (tryptophan-to-quinolinate)...
- Increasing production of homocysteine and neopterin and degradation of tryptophan with older age
Institute of Medical Chemistry and Biochemistry, Leopold Franzens University, Innsbruck, Austria
Clin Biochem 37:684-7. 2004
..Homocysteine is known to be elevated in the elderly, which is possibly due to an insufficient availability of folate, B6, and/or B12...
- CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression
C L Raison
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
Mol Psychiatry 15:393-403. 2010
Cytokine-induced activation of indoleamine 2,3-dioxygenase (IDO) catabolizes L-tryptophan (TRP) into L-kynurenine (KYN), which is metabolized to quinolinic acid (QUIN) and kynurenic acid (KA)...
- Pharmacological manipulation of kynurenic acid: potential in the treatment of psychiatric disorders
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
CNS Drugs 23:91-101. 2009
The kynurenine pathway constitutes the main route of tryptophan degradation and generates the production of several neuroactive compounds; quinolinic acid is an excitotoxic NMDA receptor agonist, 3-hydroxykynurenine is a free-radical ..
- Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice
J C O'Connor
Integrative Immunology and Behavior, Department of Animal Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana Champaign, Urbana, IL, USA
Mol Psychiatry 14:511-22. 2009
..Both minocycline and 1-MT normalize the kynurenine/tryptophan ratio in the plasma and brain of LPS-treated mice without changing the LPS-induced increase in ..
- N-formylkynurenine as a marker of high light stress in photosynthesis
Tina M Dreaden
School of Chemistry and Biochemistry and Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA
J Biol Chem 286:22632-41. 2011
..Reactive oxygen species reactions lead to oxidative damage of the reaction center, D1 protein turnover, and inhibition of electron transfer. Our results are consistent with a role for the CP43 NFK modification in photoinhibition...
- Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder
M Elizabeth Sublette
Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY 10032, United States
Brain Behav Immun 25:1272-8. 2011
..inflammatory process that has been minimally investigated in this regard is cytokine-stimulated production of kynurenine (KYN) from tryptophan (TRP)...
- Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer
Department of Internal Medicine, Hamamatsu University School of Medicine, 1 20 1 Hanadayama Higashiku, Hamamatsu, Shizuoka 431 3125, Japan
Lung Cancer 67:361-5. 2010
Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step of tryptophan (Trp) degradation along the kynurenine (Kyn) pathway. By depleting tryptophan, IDO is considered to be a fundamental immune escape mechanism for tumor cells...
- IFN-beta1b induces kynurenine pathway metabolism in human macrophages: potential implications for multiple sclerosis treatment
G J Guillemin
Centre for Immunology, St Vincent s Hospital, Sydney, Australia
J Interferon Cytokine Res 21:1097-101. 2001
..The kynurenine pathway (KP) is chiefly activated by IFN-gamma and IFN-alpha, leading to the production of a variety of ..
- Redox reactions related to indoleamine 2,3-dioxygenase and tryptophan metabolism along the kynurenine pathway
S R Thomas
The Biochemistry Group, The Heart Research Institute, Sydney, New South Wales, Australia
Redox Rep 4:199-220. 1999
..moiety of L-tryptophan (Trp) and other indoleamines and represents the initial and rate-limiting enzyme of the kynurenine (Kyn) pathway...
- The kynurenine pathway modulates neurodegeneration in a Drosophila model of Huntington's disease
Department of Genetics, University of Leicester, Leicester LE1 7RH, UK
Curr Biol 21:961-6. 2011
Neuroactive metabolites of the kynurenine pathway (KP) of tryptophan degradation have been implicated in the pathophysiology of neurodegenerative disorders, including Huntington's disease (HD) ...
- Indoleamine 2,3-dioxygenase and regulatory function: tryptophan starvation and beyond
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
Methods Mol Biol 677:269-80. 2011
..As a result, IDO(+) DCs mediate multiple effects on T lymphocytes, including inhibition of proliferation, apoptosis, and differentiation toward a regulatory phenotype...
- Tryptophan pyrrolase of rabbit intestine. D- and L-tryptophan-cleaving enzyme or enzymes
J Biol Chem 242:5260-6. 1967
- Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and beta 2-microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients
M P Heyes
Section on Analytical Biochemistry, NIMH, NIH, Bethesda, MD 20892
J Neuroimmunol 40:71-80. 1992
..acid (QUIN) is an neurotoxic N-methyl-D-aspartate receptor agonist and an L-tryptophan metabolite of the kynurenine pathway...
- The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function
Mariella Della Chiesa
DIMS Dipartimento di Medicina Sperimentale, Universita di Genova, Genova, Italy
Blood 108:4118-25. 2006
..In this study, we also demonstrate that natural killer (NK)-cell function can be influenced by IDO. Indeed, l-kynurenine, a Trp-derived catabolite resulting from IDO activity, was found to prevent the cytokine-mediated up-regulation ..
- Increased indoleamine 2,3-dioxygenase (IDO) activity and elevated serum levels of tryptophan catabolites in patients with chronic kidney disease: a possible link between chronic inflammation and uraemic symptoms
Jörg C Schefold
Department of Nephrology and Intensive Care, Charite University Medicine, Campus Virchow Clinic, Berlin, Germany
Nephrol Dial Transplant 24:1901-8. 2009
..Here we investigate Trp catabolism, IDO activity and the role of inflammation in moderate to very severe CKD and haemodialysis...
- HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20815, USA
Blood 109:3351-9. 2007
..enzyme that inhibits T-cell proliferation by catabolizing the essential amino acid tryptophan (Trp) into the kynurenine (kyn) pathway...
- Tryptophan as a link between psychopathology and somatic states
Department of Biological Psychiatry, University Hospital Groningen, The Netherlands
Psychosom Med 65:665-71. 2003
..Several somatic illnesses are associated with psychiatric comorbidity. Evidence is provided that availability of the essential amino acid tryptophan, which is the precursor of serotonin, may cause this phenomenon...
- The activity of the immunoregulatory enzyme indoleamine 2,3-dioxygenase is decreased in smokers
Department of Microbiology and Immunology, University of Tampere, Medical School, Tampere, Finland
Clin Exp Immunol 145:469-73. 2006
..IDO), an enzyme involved in the degradation of the essential amino acid tryptophan (trp) to its main metabolite kynurenine (kyn), suppresses T cell activity...
- The kynurenine pathway of tryptophan degradation as a drug target
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA
Curr Opin Pharmacol 4:12-7. 2004
In mammalian cells, the essential amino acid tryptophan is degraded primarily by the kynurenine pathway, a cascade of enzymatic steps containing several biologically active compounds...
- Concurrent quantification of quinolinic, picolinic, and nicotinic acids using electron-capture negative-ion gas chromatography-mass spectrometry
G A Smythe
Ray Williams Biomedical Mass Spectrometry Facility, UNSW, Wallace Wurth Building, Faculty of Medicine, Sydney, New South Wales, 2052, Australia
Anal Biochem 301:21-6. 2002
Quinolinic, picolinic, and nicotinic acids and nicotinamide are end products of the kynurenine pathway from l-tryptophan and are intermediates in the biosynthesis of nicotinamide adenine dinucleotide...
- Expression of the kynurenine pathway enzymes in human microglia and macrophages
Gilles J Guillemin
Centre for Immunology, St Vincent s Hospital, Sydney, Australia
Adv Exp Med Biol 527:105-12. 2003
There is good evidence that the kynurenine pathway (KP) and one of its products, quinolinic acid (QUIN) play a role in the pathogenesis of neurological diseases. Monocytic cells are known to be the major producers of QUIN...
- A community-based study on determinants of circulating markers of cellular immune activation and kynurenines: the Hordaland Health Study
Section for Pharmacology, University of Bergen, Norway
Clin Exp Immunol 173:121-30. 2013
Circulating neopterin and kynurenine/tryptophan ratio (KTR) increase during inflammation and serve as markers of cellular immune activation, but data are sparse on other determinants of these markers and metabolites of the kynurenine ..
- KynR, a Lrp/AsnC-type transcriptional regulator, directly controls the kynurenine pathway in Pseudomonas aeruginosa
Claire A Knoten
Department of Microbiology and Immunology, The Brody School of Medicine at East Carolina University, 600 Moye Blvd, Greenville, NC 27834, USA
J Bacteriol 193:6567-75. 2011
..P. aeruginosa is part of a small group of bacteria that use the kynurenine pathway to catabolize tryptophan...
- Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys
Molecular Endocrinology and Oncology Research Center, CHUQ, CHUL Pavillon and Faculty of Pharmacy, Laval University, Quebec, PQ, Canada
Behav Brain Res 186:161-7. 2008
..KYNA synthesis was stimulated by prolonged systemic administration of the kynurenine 3-hydroxylase inhibitor Ro 61-8048...
- Functional characterization and mechanism of action of recombinant human kynurenine 3-hydroxylase
Department of Biology, Pharmacia and Upjohn, Nerviano, Italy
Eur J Biochem 267:1092-9. 2000
The mitochondrial outer membrane enzyme kynurenine 3-hydroxylase (K3H) is an NADPH-dependent flavin mono-oxygenase involved in the tryptophan pathway, where it catalyzes the hydroxylation of kynurenine...
- Comparative effects of oxygen on indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway
Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA
Free Radic Biol Med 28:615-24. 2000
..These enzymes catalyze the rate-limiting step in the kynurenine (KYN) pathway from trp to quinolinic acid (QA) with TDO in kidney and liver and IDO in many tissues, including ..
- Cinnabarinic acid, an endogenous metabolite of the kynurenine pathway, activates type 4 metabotropic glutamate receptors
Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy
Mol Pharmacol 81:643-56. 2012
Cinnabarinic acid is an endogenous metabolite of the kynurenine pathway that meets the structural requirements to interact with glutamate receptors...
- Kynurenine concentration of serum was increased by exercise
Department of Physiology, School of Health Sciences, Fujita Health University, Aichi, Japan
Adv Exp Med Biol 467:717-22. 1999
b>Kynurenine pathway of tryptophan makes a lot of physiological active substances, such as quinolinate, NAD and so on, suggesting that kynurenine itself may play a very important role physiologically...
- Tryptophan depletion in depressed patients occurs independent of kynurenine pathway activation
Martina M Hughes
Neuroimmunology Research Group, Department of Physiology, School of Medicine and Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland
Brain Behav Immun 26:979-87. 2012
The kynurenine pathway (KP) and its rate-limiting tryptophan degrading enzyme indolamine 2,3-dioxygenase (IDO) have been implicated in the pathogenesis of depression...
- Mechanism of increases in L-kynurenine and quinolinic acid in renal insufficiency
Department of Laboratory Medicine, Gifu University School of Medicine, Gifu 500 8705, Japan
Am J Physiol Renal Physiol 279:F565-72. 2000
Marked increases in metabolites of the L-tryptophan-kynurenine pathway, L-kynurenine and quinolinic acid (Quin), were observed in serum and cerebrospinal fluid (CSF) of both the rat and human with renal insufficiency...
- Structural basis of kynurenine 3-monooxygenase inhibition
Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK
Nature 496:382-5. 2013
Inhibition of kynurenine 3-monooxygenase (KMO), an enzyme in the eukaryotic tryptophan catabolic pathway (that is, kynurenine pathway), leads to amelioration of Huntington's-disease-relevant phenotypes in yeast, fruitfly and mouse models, ..
- Low plasma vitamin B-6 status affects metabolism through the kynurenine pathway in cardiovascular patients with systemic inflammation
Bevital A S, Laboratoriebygget, 5021 Bergen, Norway
J Nutr 141:611-7. 2011
..for suspected coronary heart disease, we investigated if plasma concentrations of any metabolites in the kynurenine pathway, which depend on PLP as cofactor, may serve as metabolic marker(s) of vitamin B-6 status...
- The kynurenine pathway in brain tumor pathogenesis
Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia
Cancer Res 72:5649-57. 2012
..The kynurenine pathway (KP) is the principal route of L-tryptophan catabolism leading to the formation of the essential ..
- An expanding range of targets for kynurenine metabolites of tryptophan
Trevor W Stone
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
Trends Pharmacol Sci 34:136-43. 2013
The kynurenine pathway of tryptophan metabolism accounts for most of the tryptophan that is not committed to protein synthesis and includes compounds active in the nervous and immune systems...
- Perinatal kynurenine 3-hydroxylase inhibition in rodents: pathophysiological implications
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA
J Neurosci Res 85:845-54. 2007
The kynurenine pathway (KP) of tryptophan degradation contains three neuroactive metabolites: the neuroinhibitory agent kynurenic acid (KYNA) and, in a competing branch, the free radical generator 3-hydroxykynurenine (3-HK) and the ..
- Changes in kynurenine pathway metabolism in the brain, liver and kidney of aged female Wistar rats
University of New South Wales, Faculty of Medicine, Sydney, NSW, Australia
FEBS J 278:4425-34. 2011
The kynurenine pathway of tryptophan catabolism plays an important role in several biological systems affected by aging...
- Growth inhibition of multiresistant enterococci by interferon-gamma-activated human uro-epithelial cells
C R MacKenzie
Institute for Medical Microbiology and Virology, Heinrich Heine University, Dusseldorf, Germany
J Med Microbiol 48:935-41. 1999
..analysis, at translational level by Western blot and also at a functional level by L-tryptophan degradation to L-kynurenine -- in the uro-epithelial cell line RT4...
- The association of the kynurenine pathway of tryptophan metabolism with acute brain dysfunction during critical illness*
Jessica R Adams Wilson
Vanderbilt University School of Medicine, Nashville, TN, USA
Crit Care Med 40:835-41. 2012
..has been linked to the pathogenesis of other neurocognitive diseases through metabolism to neurotoxins via the kynurenine pathway, a role for kynurenine pathway activity in intensive care unit brain dysfunction (delirium and coma) ..
- Kynurenine pathway and disease: an overview
Verónica Pérez-De La Cruz
Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, S S A, Mexico
CNS Neurol Disord Drug Targets 6:398-410. 2007
b>Kynurenine pathway is gaining more and more attention every day in biomedical research since this catabolic route for tryptophan decomposition is not only implicated in different neurological disorders, but also possesses neuroactive ..
- Pre- and postnatal exposure to kynurenine causes cognitive deficits in adulthood
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
Eur J Neurosci 35:1605-12. 2012
..To this end, we stimulated KYNA formation by adding the KYNA precursor kynurenine (100 mg/day) to the chow fed to rat dams from gestational day 15 to postnatal day 21 (PD 21)...
- Highlights at the gate of tryptophan catabolism: a review on the mechanisms of activation and regulation of indoleamine 2,3-dioxygenase (IDO), a novel target in cancer disease
Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06123 Perugia, Italy
Amino Acids 37:219-29. 2009
Indoleamine 2,3-dioxygenase (IDO) catalyzes the first and rate-limiting step of Kynurenine pathway along the major route of Tryptophan catabolism...
- Effects of kynurenine metabolites on mesangial cell proliferation and gene expression
Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co, Ltd, Saitama shi, Saitama, Japan
Exp Mol Pathol 87:70-5. 2009
In the present study, we examined the effects of kynurenine metabolites on cultured mesangial cells (MCs) and demonstrated for the first time that they affect MC proliferation and gene expression...
- The kynurenine pathway in major depression: haplotype analysis of three related functional candidate genes
University Psychiatric Center K U Leuven, Campus Gasthuisberg, Leuven, Belgium
Psychiatry Res 188:355-60. 2011
..One of the relevant metabolic pathways in this regard is the kynurenine pathway...
- Singlet-oxygen-mediated amino acid and protein oxidation: formation of tryptophan peroxides and decomposition products
The Heart Research Institute, Camperdown, NSW 2050, Australia
Free Radic Biol Med 47:92-102. 2009
..This approach may allow the quantification of protein modification in intact cells arising from singlet oxygen formation...
- Anti-infectious activity of tryptophan metabolites in the L-tryptophan-L-kynurenine pathway
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan
Biol Pharm Bull 32:41-4. 2009
..05). When the antimicrobial activity of the tryptophan metabolites in the L-tryptophan-L-kynurenine pathway was examined, 3-hydroxy-DL-kynurenine and alpha-picolinic acid had strong antibacterial activity against ..
- The possible role of the kynurenine pathway in adolescent depression with melancholic features
NYU Child Study Center, Child and Adolescent Psychiatry, New York University School of Medicine, NY 10016, USA
J Child Psychol Psychiatry 51:935-43. 2010
..MDD with and without melancholic features (M-MDD and NonM-MDD) have distinct biological features in the kynurenine pathway (KP)...
- Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in Schizophrenia
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, PO Box 21247, Baltimore, MD 21228, USA
Schizophr Bull 36:211-8. 2010
The brain concentration of kynurenic acid (KYNA), a metabolite of the kynurenine pathway of tryptophan degradation and antagonist at both the glycine coagonist site of the N-methyl-D-aspartic acid receptor (NMDAR) and the alpha7 nicotinic ..
- Indoleamine 2,3-dioxygenase and 3-hydroxykynurenine modifications are found in the neuropathology of Alzheimer's disease
David J Bonda
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
Redox Rep 15:161-8. 2010
Tryptophan metabolism, through the kynurenine pathway, produces neurotoxic intermediates that are implicated in the pathogenesis of Alzheimer's disease...
- High activity of indoleamine 2,3 dioxygenase enzyme predicts disease severity and case fatality in bacteremic patients
Department of Internal Medicine, Tampere University Hospital, University of Tampere Medical School, University of Tampere, Tampere, Finland
Shock 33:149-54. 2010
..The serum concentrations of trp and its metabolite kynurenine (kyn) were measured by reverse-phase high-performance liquid chromatography 1 to 4 days after the positive blood ..
- Indoleamine 2,3-dioxigenase (IDO) is critical for host resistance against Trypanosoma cruzi
Carolina Paola Knubel
Centro de Investigaciones en Bioquímica Clínica e Inmunología Consejo Nacional de Investigaciones Científicas y Tecnicas, Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, 5000, Argentina
FASEB J 24:2689-701. 2010
..cruzi amastigotes were sensitive to L-kynurenine downstream metabolites 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid, while 3-HK also affected the ..
- Comparative profiling of the mammalian mitochondrial proteome: multiple aconitase-2 isoforms including N-formylkynurenine modifications as part of a protein biomarker signature for reactive oxidative species
ProteoSys AG, Carl Zeiss Strasse 51, 55129 Mainz, Germany
J Proteome Res 5:625-33. 2006
..g., reactive oxygen species (ROS), which induce N-formyl-kynurenine from oxidized tryptophans in certain mitochondrial proteins which are localized in close spatial proximity to ..
- Evidence for a key role of the peripheral kynurenine pathway in the modulation of anxiety- and depression-like behaviours in mice: focus on individual differences
UMRS Inserm U930, CNRS ERL 3106, Département des sciences du comportement, Universite Francois Rabelais, Tours, France
Pharmacol Biochem Behav 98:161-8. 2011
..to the Unpredictable Chronic Mild Stress procedure (UCMS) resulted in peripheral and cerebral alterations of the kynurenine pathway (KP)...
- Sputum indoleamine-2, 3-dioxygenase activity is increased in asthmatic airways by using inhaled corticosteroids
Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
J Allergy Clin Immunol 121:43-50. 2008
..IDO inhibits eosinophilic inflammation in a murine asthma model, but little is known about its role in asthmatic patients or the effects of corticosteroids on this key regulatory enzyme...
- A small-molecule screen identifies L-kynurenine as a competitive inhibitor of TAA1/TAR activity in ethylene-directed auxin biosynthesis and root growth in Arabidopsis
State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Peking Tsinghua Center for Life Sciences, Beijing 100871, China
Plant Cell 23:3944-60. 2011
..Using a chemical biology approach, we identified a small molecule, l-kynurenine (Kyn), which effectively inhibited ethylene responses in Arabidopsis thaliana root tissues...
- Plasma kynurenine and related measures in tic disorder patients
Pieter J Hoekstra
Department of Psychiatry, University Medical Center Groningen, University of Groningen, P O Box 660, 9700 AR, Groningen, The Netherlands
Eur Child Adolesc Psychiatry 16:71-7. 2007
Increased plasma kynurenine has been reported in tic disorder patients, and this observation has been suggested to be indicative of immune dysregulation...
- An observational cohort study of the kynurenine to tryptophan ratio in sepsis: association with impaired immune and microvascular function
Christabelle J Darcy
Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia
PLoS ONE 6:e21185. 2011
..indoleamine 2,3-dioxygenase (IDO) which metabolizes the essential amino acid tryptophan to the toxic metabolite kynurenine. IDO can be expressed in endothelial cells, hepatocytes and mononuclear leukocytes, all of which contribute to ..
- Neuropharmacology of quinolinic and kynurenic acids
T W Stone
Department of Pharmacology, University of Glasgow, Scotland
Pharmacol Rev 45:309-79. 1993
In a little more than 10 years, the kynurenine metabolites of tryptophan have emerged from their former position as biochemical curiosities, to occupy a prominent position in research on the causes and treatment of several major CNS ..
- The astrocyte-derived alpha7 nicotinic receptor antagonist kynurenic acid controls extracellular glutamate levels in the prefrontal cortex
Hui Qiu Wu
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA
J Mol Neurosci 40:204-10. 2010
..we show here that nanomolar concentrations of KYNA, infused directly or produced in situ from its bioprecursor kynurenine, significantly decrease extracellular glutamate levels in the prefrontal cortex...
- Kynurenine and its metabolites in Alzheimer's disease patients
Department of Geriatrics, Medical University, Bialystok, Poland
Adv Med Sci 55:204-11. 2010
The kynurenine pathway (KP) is a major route of tryptophan metabolism. Several metabolites of this pathway are proposed to be involved in the pathogenesis of Alzheimer's disease...
- Neuroprotective effect of L-kynurenine sulfate administered before focal cerebral ischemia in mice and global cerebral ischemia in gerbils
Division of Preclinical Research, EGIS Pharmaceuticals Plc, Budapest, Hungary
Eur J Pharmacol 564:116-22. 2007
..The neuroprotective effect of L-kynurenine sulfate, a precursor of kynurenic acid, was therefore studied because L-kynurenine readily crosses the blood-..
- Kynurenines in the CNS: from endogenous obscurity to therapeutic importance
T W Stone
Institute of Biomedical and Life Sciences, University West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK
Prog Neurobiol 64:185-218. 2001
In just under 20 years the kynurenine family of compounds has developed from a group of obscure metabolites of the essential amino acid tryptophan into a source of intensive research, with postulated roles for quinolinic acid in ..
- Development and therapeutic potential of kynurenic acid and kynurenine derivatives for neuroprotection
T W Stone
Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow, UK
Trends Pharmacol Sci 21:149-54. 2000
Manipulation of the kynurenine pathway of tryptophan metabolism has yielded a plethora of agents that are now being developed as neuroprotectants and anticonvulsants...
- Indoleamine 2,3-dioxygenase-2; a new enzyme in the kynurenine pathway
Helen J Ball
Discipline of Pathology and Bosch Institute, University of Sydney, Camperdown, NSW 2006, Australia
Int J Biochem Cell Biol 41:467-71. 2009
The kynurenine pathway of tryptophan metabolism converts the amino acid tryptophan into a number of biologically active metabolites...
- Indoleamine 2,3-dioxygenase in infection: the paradox of an evasive strategy that benefits the host
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
Microbes Infect 11:133-41. 2009
..This review deals with recent findings that could gain IDO a reputation of Jack-of-all-trades in mammalian host/microbe interactions...
- l-kynurenine combined with probenecid and the novel synthetic kynurenic acid derivative attenuate nitroglycerin-induced nNOS in the rat caudal trigeminal nucleus
Department of Neurology, University of Szeged, Szeged, Hungary
Neuropharmacology 57:425-9. 2009
..play a crucial role in trigeminal pain processing, the aim of our experiments was to compare the effects of L-kynurenine (L-KYN) combined with probenecid (PROB) or with 2-(2-N,N-dimethylaminoethylamine-1-carbonyl)-1H-quinolin-4-one ..
- Indoleamine 2,3-dioxygenase activity in nonagenarians is markedly increased and predicts mortality
Department of Microbiology and Immunology, University of Tampere, Medical School, Finland
Mech Ageing Dev 127:497-9. 2006
Indoleamine 2,3-dioxygenase (IDO), an enzyme degrading tryptophan (trp) to kynurenine (kyn), suppresses T cell activity. Ageing of the immune system, immunosenescence, includes a decline in T cell function...
- Increased plasma kynurenine values and kynurenine-tryptophan ratios after major trauma are early indicators for the development of sepsis
Tim T Lögters
Department of Trauma and Hand Surgery, University Hospital Dusseldorf, Germany
Shock 32:29-34. 2009
b>Kynurenine, the major degradation product of tryptophan has been shown to directly damage tissues, but its possible contribution to posttraumatic morbidity is unknown...
- Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation
Department of Psychiatry, University Hospital of Maastricht, Postbus 5800, 6202 AZ Maastricht, The Netherlands
Life Sci 71:1837-48. 2002
..The aims of the present study were to examine the effects of pregnancy and delivery on plasma kynurenine, a major tryptophan catabolite synthesized after induction of indoleamine-2, 3 dioxygenase (IDO) by pro-..
- The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation
Division of Hematology Oncology, Blood and Marrow Transplantation, Department of Pediatrics and The Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA
J Immunol 181:5396-404. 2008
..Adding kynurenine, the immediate downstream metabolite of tryptophan, bypasses the 1-methyl-D-tryptophan effect and restores PDC-..