Tryptophan kynurenine pathway in post-COVID syndrome (Homo sapiens)

From WikiPathways

Jump to: navigation, search
ArcPathVisio Brace Ellipse EndoplasmicReticulum GolgiApparatus HexagonPathVisio MimDegradation Mitochondria Octagon PentagonPathVisio Rectangle RoundedRectangle SarcoplasmicReticulum TriangleEquilateralEast TrianglePathVisio none Neuronal damage - ExcitotoxicityPro-inflammatory and Neuroactive Tryptophan CatabolitesPost Covidpro-inflammatory responses and apoptosis of neurons and astrocytesAhRPresistent InflammationAnti-inflammatoryComplex IComplex IIDDCIDO2Anthranilic acidTNFAADATKMOKynurenineIL1BIFNB1IL6AFMIDOxidative Damage ResponseN-Formylkynurenine3-Hydroxykynurenine3-Hydroxyanthranilic acidHAAOXanthurenic acidNeuroinflammationTryptophanIDO1TDO23-HydroxykynurenamineQuinolinic acidKynurenic AcidKYAT1KYAT2KYAT3KYAT4KYNUH2O2IFNGROSComplex IVComplex IIComplex IComplex IIIComplex IIComplex IBlood Brain BarrierdisruptionOxidative Damage ResponseOxidative Damage ResponseDecreased mitochondrial oxidative phosphorylationDecreased mitochondrial oxidative phosphorylationApoptosisApoptosisTNFIFNA6IFNGIL1BIFNB1KYNUName: Tryptophan kynurenine pathway in post-COVID syndromeOrganism: Homo sapiens


Description

Following the SARS-CoV-2 pandemic, increasing evidence suggests that the overactivation of the tryptophan-kynurenine pathway (TKP) plays a significant role in the pathophysiology of post-COVID syndrome (PCS). This dysregulation is marked by reduced tryptophan (TRP) levels and elevated concentrations of specific tryptophan catabolites (TRYCATs). Notably, heightened TKP activity has been observed in patients exhibiting symptoms of post-acute sequelae of COVID-19 (PASC). In fact, elevated levels of TKP metabolites such as quinolinic acid, 3- hydroxy anthranilic acid and kynurenine, have been associated with cognitive impairments. Persistent inflammatory conditions observed in Post-Covid patients potentially upregulate the indoleamine 2,3-dioxygenase (IDO) enzymes, specifically IDO 1, as well as KMO, which catalyses the conversion from Kynurenine to 3-Hydroxykynurenine. Thus, the kynurenine pathway relates to PACS and potentially enables future biomarker and therapeutic possibilities.

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Image:Wplogo_31.pngCommunity: COVID-19
Image:Curated.pngApproved version

Ontology Terms

Bibliography

View all...
  1. Fujigaki H, Yamamoto Y, Saito K; ''L-Tryptophan-kynurenine pathway enzymes are therapeutic target for neuropsychiatric diseases: Focus on cell type differences.''; Neuropharmacology, 2017 PubMed Europe PMC Scholia
  2. Yeung AW, Terentis AC, King NJ, Thomas SR; ''Role of indoleamine 2,3-dioxygenase in health and disease.''; Clin Sci (Lond), 2015 PubMed Europe PMC Scholia
  3. Goldstein LE, Leopold MC, Huang X, Atwood CS, Saunders AJ, Hartshorn M, Lim JT, Faget KY, Muffat JA, Scarpa RC, Chylack LT Jr, Bowden EF, Tanzi RE, Bush AI; ''3-Hydroxykynurenine and 3-hydroxyanthranilic acid generate hydrogen peroxide and promote alpha-crystallin cross-linking by metal ion reduction.''; Biochemistry, 2000 PubMed Europe PMC Scholia
  4. Campbell BM, Charych E, Lee AW, Möller T; ''Kynurenines in CNS disease: regulation by inflammatory cytokines.''; Front Neurosci, 2014 PubMed Europe PMC Scholia
  5. Lugo-Huitrón R, Ugalde Muñiz P, Pineda B, Pedraza-Chaverrí J, Ríos C, Pérez-de la Cruz V; ''Quinolinic acid: an endogenous neurotoxin with multiple targets.''; Oxid Med Cell Longev, 2013 PubMed Europe PMC Scholia
  6. O'Farrell K, Harkin A; ''Stress-related regulation of the kynurenine pathway: Relevance to neuropsychiatric and degenerative disorders.''; Neuropharmacology, 2017 PubMed Europe PMC Scholia
  7. Peluso MJ, Lu S, Tang AF, Durstenfeld MS, Ho HE, Goldberg SA, Forman CA, Munter SE, Hoh R, Tai V, Chenna A, Yee BC, Winslow JW, Petropoulos CJ, Greenhouse B, Hunt PW, Hsue PY, Martin JN, Daniel Kelly J, Glidden DV, Deeks SG, Henrich TJ; ''Markers of Immune Activation and Inflammation in Individuals With Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.''; J Infect Dis, 2021 PubMed Europe PMC Scholia
  8. Smith JR, Jamie JF, Guillemin GJ; ''Kynurenine-3-monooxygenase: a review of structure, mechanism, and inhibitors.''; Drug Discov Today, 2016 PubMed Europe PMC Scholia
  9. Cysique LA, Jakabek D, Bracken SG, Allen-Davidian Y, Heng B, Chow S, Dehhaghi M, Staats Pires A, Darley DR, Byrne A, Phetsouphanh C, Kelleher A, Dore GJ, Matthews GV, Guillemin GJ, Brew BJ; ''The kynurenine pathway relates to post-acute COVID-19 objective cognitive impairment and PASC.''; Ann Clin Transl Neurol, 2023 PubMed Europe PMC Scholia
  10. Sathyasaikumar KV, Tararina M, Wu HQ, Neale SA, Weisz F, Salt TE, Schwarcz R; ''Xanthurenic Acid Formation from 3-Hydroxykynurenine in the Mammalian Brain: Neurochemical Characterization and Physiological Effects.''; Neuroscience, 2017 PubMed Europe PMC Scholia
  11. Mona Dehhaghi, Hamed Kazemi Shariat Panahi, Gilles J Guillemin; ''Microorganisms, Tryptophan Metabolism, and Kynurenine Pathway: A Complex Interconnected Loop Influencing Human Health Status''; Int J Tryptophan Res., 2019 PubMed Europe PMC Scholia
  12. Okuda S, Nishiyama N, Saito H, Katsuki H; ''Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine.''; Proc Natl Acad Sci U S A, 1996 PubMed Europe PMC Scholia
  13. Vogel CF, Goth SR, Dong B, Pessah IN, Matsumura F; ''Aryl hydrocarbon receptor signaling mediates expression of indoleamine 2,3-dioxygenase.''; Biochem Biophys Res Commun, 2008 PubMed Europe PMC Scholia
  14. Taylor MW, Feng GS; ''Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism.''; FASEB J, 1991 PubMed Europe PMC Scholia
  15. Wirthgen E, Hoeflich A, Rebl A, Günther J; ''Kynurenic Acid: The Janus-Faced Role of an Immunomodulatory Tryptophan Metabolite and Its Link to Pathological Conditions.''; Front Immunol, 2017 PubMed Europe PMC Scholia
  16. Qian Han, Tao Cai, Danilo A. Tagle, Jianyong Li; ''Structure, expression, and function of kynurenine aminotransferases in human and rodent brains''; Cell Mol Life Sci., 2010 PubMed Europe PMC Scholia
  17. Behan WM, McDonald M, Darlington LG, Stone TW; ''Oxidative stress as a mechanism for quinolinic acid-induced hippocampal damage: protection by melatonin and deprenyl.''; Br J Pharmacol, 1999 PubMed Europe PMC Scholia
  18. Maitre M, Taleb O, Jeltsch-David H, Klein C, Mensah-Nyagan AG; ''Xanthurenic acid: A role in brain intercellular signaling.''; J Neurochem, 2024 PubMed Europe PMC Scholia
  19. Stein A, Simnica D, Schultheiß C, Scholz R, Tintelnot J, Gökkurt E, von Wenserski L, Willscher E, Paschold L, Sauer M, Lorenzen S, Riera-Knorrenschild J, Depenbusch R, Ettrich TJ, Dörfel S, Al-Batran SE, Karthaus M, Pelzer U, Waberer L, Hinke A, Bauer M, Massa C, Seliger B, Wickenhauser C, Bokemeyer C, Hegewisch-Becker S, Binder M; ''PD-L1 targeting and subclonal immune escape mediated by PD-L1 mutations in metastatic colorectal cancer.''; J Immunother Cancer, 2021 PubMed Europe PMC Scholia
  20. Chen Y, Zhang J, Yang Y, Xiang K, Li H, Sun D, Chen L; ''Kynurenine-3-monooxygenase (KMO): From its biological functions to therapeutic effect in diseases progression.''; J Cell Physiol, 2022 PubMed Europe PMC Scholia
  21. Phillips RS; ''Structure and mechanism of kynureninase.''; Arch Biochem Biophys, 2014 PubMed Europe PMC Scholia
  22. Oxenkrug G, van der Hart M, Roeser J, Summergrad P; ''Anthranilic Acid: A Potential Biomarker and Treatment Target for Schizophrenia.''; Ann Psychiatry Ment Health, 2016 PubMed Europe PMC Scholia
  23. Jhamandas KH, Boegman RJ, Beninger RJ, Miranda AF, Lipic KA; ''Excitotoxicity of quinolinic acid: modulation by endogenous antagonists.''; Neurotox Res, 2000 PubMed Europe PMC Scholia
  24. Zádor F, Joca S, Nagy-Grócz G, Dvorácskó S, Szűcs E, Tömböly C, Benyhe S, Vécsei L; ''Pro-Inflammatory Cytokines: Potential Links between the Endocannabinoid System and the Kynurenine Pathway in Depression.''; Int J Mol Sci, 2021 PubMed Europe PMC Scholia
  25. Morita T, Saito K, Takemura M, Maekawa N, Fujigaki S, Fujii H, Wada H, Takeuchi S, Noma A, Seishima M; ''3-Hydroxyanthranilic acid, an L-tryptophan metabolite, induces apoptosis in monocyte-derived cells stimulated by interferon-gamma.''; Ann Clin Biochem, 2001 PubMed Europe PMC Scholia
  26. Braidy N, Grant R, Adams S, Brew BJ, Guillemin GJ; ''Mechanism for quinolinic acid cytotoxicity in human astrocytes and neurons.''; Neurotox Res, 2009 PubMed Europe PMC Scholia
  27. Kan Gao, Chun-Long Mu, Aitak Farzi, Wei-Yun Zhu; ''Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain''; Adv Nutr ., 2020 PubMed Europe PMC Scholia
  28. Pfefferkorn ER, Rebhun S, Eckel M; ''Characterization of an indoleamine 2,3-dioxygenase induced by gamma-interferon in cultured human fibroblasts.''; J Interferon Res, 1986 PubMed Europe PMC Scholia
  29. Schuck PF, Tonin A, da Costa Ferreira G, Viegas CM, Latini A, Duval Wannmacher CM, de Souza Wyse AT, Dutra-Filho CS, Wajner M; ''Kynurenines impair energy metabolism in rat cerebral cortex.''; Cell Mol Neurobiol, 2007 PubMed Europe PMC Scholia
  30. Tanaka M, Tóth F, Polyák H, Szabó Á, Mándi Y, Vécsei L; ''Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway.''; Biomedicines, 2021 PubMed Europe PMC Scholia
  31. Malherbe P, Köhler C, Da Prada M, Lang G, Kiefer V, Schwarcz R, Lahm HW, Cesura AM; ''Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase.''; J Biol Chem, 1994 PubMed Europe PMC Scholia
  32. Camille Martin-Gallausiaux, Pierre Larraufie, Anne Jarry, Fabienne Béguet-Crespe, Ludovica Marinelli, Florence Ledue, Frank Reimann, Hervé M Blottière, Nicolas Lapaque; ''Butyrate Produced by Commensal Bacteria Down-Regulates Indolamine 2,3-Dioxygenase 1 ( IDO-1) Expression via a Dual Mechanism in Human Intestinal Epithelial Cells''; Front Immunol., 2018 PubMed Europe PMC Scholia
  33. Kubicova L, Hadacek F, Bachmann G, Weckwerth W, Chobot V; ''Coordination Complex Formation and Redox Properties of Kynurenic and Xanthurenic Acid Can Affect Brain Tissue Homeodynamics.''; Antioxidants (Basel), 2019 PubMed Europe PMC Scholia
  34. Savitz J; ''The kynurenine pathway: a finger in every pie.''; Mol Psychiatry, 2020 PubMed Europe PMC Scholia
  35. Dolšak A, Gobec S, Sova M; ''Indoleamine and tryptophan 2,3-dioxygenases as important future therapeutic targets.''; Pharmacol Ther, 2021 PubMed Europe PMC Scholia
  36. Clement CC, D'Alessandro A, Thangaswamy S, Chalmers S, Furtado R, Spada S, Mondanelli G, Ianni F, Gehrke S, Gargaro M, Manni G, Cara LCL, Runge P, Tsai WL, Karaman S, Arasa J, Fernandez-Rodriguez R, Beck A, Macchiarulo A, Gadina M, Halin C, Fallarino F, Skobe M, Veldhoen M, Moretti S, Formenti S, Demaria S, Soni RK, Galarini R, Sardella R, Lauvau G, Putterman C, Alitalo K, Grohmann U, Santambrogio L; ''3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine.''; Nat Commun, 2021 PubMed Europe PMC Scholia
  37. G Clarke, S Grenham, P Scully, P Fitzgerald, R D Moloney, F Shanahan, T G Dinan, J F Cryan; ''The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner''; Mol Psychiatry, 2013 PubMed Europe PMC Scholia
  38. Dobrovolsky VN, Bowyer JF, Pabarcus MK, Heflich RH, Williams LD, Doerge DR, Arvidsson B, Bergquist J, Casida JE; ''Effect of arylformamidase (kynurenine formamidase) gene inactivation in mice on enzymatic activity, kynurenine pathway metabolites and phenotype.''; Biochim Biophys Acta, 2005 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
139215
Approved
view00:46, 26 May 2025EweitzModified description
139214view00:45, 26 May 2025EweitzModified title
139204view06:31, 25 May 2025EgonwRemoved two stock comments
139140view08:38, 23 May 2025Kristof-KirpsUpdated all Gene product identifiers
139139view08:28, 23 May 2025Kristof-KirpsStarted changing Identifiers to Uniprot-Trembl
139087view11:34, 19 May 2025Kristof-KirpsOntology Term : 'tryptophan metabolic pathway' added !
139086view11:32, 19 May 2025Kristof-KirpsOntology Term : 'kynurenine metabolic pathway' added !
139085view11:27, 19 May 2025Kristof-KirpsOntology Term : 'nervous system disease pathway' added !
139084view11:26, 19 May 2025Kristof-KirpsOntology Term : 'immune system disease pathway' added !
139083view11:26, 19 May 2025Kristof-KirpsOntology Term : 'mild cognitive impairment' added !
139082view11:25, 19 May 2025Kristof-KirpsOntology Term : 'long COVID' added !
139081
COVID
view11:21, 19 May 2025Kristof-KirpsModified title
139080view11:19, 19 May 2025Kristof-KirpsNew pathway

External references

DataNodes

View all...
Name  ↓Type  ↓Database reference  ↓Comment  ↓
3-Hydroxyanthranilic acidMetaboliteHMDB01476 (HMDB)
3-HydroxykynurenamineMetaboliteHMDB0060281 (HMDB) 3-Hydroxykynurenamine
3-HydroxykynurenineMetaboliteCHEBI:1547 (ChEBI)
AADATGeneProductQ8N5Z0 (Uniprot-TrEMBL) KYAT2 = AADAT
AFMIDGeneProductQ63HM1 (Uniprot-TrEMBL)
Anthranilic acidMetaboliteCHEBI:30754 (ChEBI)
ApoptosisPathwayWP1772 (WikiPathways)
DDCGeneProductP20711 (Uniprot-TrEMBL)
  • catalyzes the decarboxylation of aromatic L-amino acids to their amine derivative
  • AADC (Aromatic L-amino acid decarboxylase)
Decreased mitochondrial oxidative phosphorylationPathwayWP111 (WikiPathways)
H2O2MetaboliteCHEBI:16240 (ChEBI)
HAAOGeneProductP46952 (Uniprot-TrEMBL)
IDO1GeneProductP14902 (Uniprot-TrEMBL) OCR lexicon match: IDO
IDO2GeneProductQ6ZQW0 (Uniprot-TrEMBL)
IFNA6GeneProductP05013 (Uniprot-TrEMBL)
IFNB1GeneProductP01574 (Uniprot-TrEMBL)
IFNG GeneProductP01579 (Uniprot-TrEMBL)
IL1BGeneProductP01584 (Uniprot-TrEMBL)
IL6GeneProductP05231 (Uniprot-TrEMBL)
KMOGeneProductO15229 (Uniprot-TrEMBL)
KYAT1ProteinQ16773 (Uniprot-TrEMBL) KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1
KYAT2ProteinQ8N5Z0 (Uniprot-TrEMBL) KAT II/aminoadipate aminotransferase
KYAT3ProteinQ6YP21 (Uniprot-TrEMBL) KAT III/cysteine conjugate beta-lyase 2
KYAT4ProteinP00505 (Uniprot-TrEMBL) KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase
KYNUGeneProductQ16719 (Uniprot-TrEMBL)
Kynurenic AcidMetaboliteCHEBI:18344 (ChEBI)
KynurenineMetaboliteCHEBI:28683 (ChEBI)
N-FormylkynurenineMetaboliteCHEBI:30249 (ChEBI)
NeuroinflammationPathwayWP4919 (WikiPathways)
Oxidative Damage ResponsePathwayWP3941 (WikiPathways)
Oxidative Damage ResponsePathwayWP3941 (WikiPathways)
Quinolinic acidMetaboliteHMDB00232 (HMDB)
TDO2GeneProductP48775 (Uniprot-TrEMBL) OCR lexicon match: TDO
TNFGeneProductP01375 (Uniprot-TrEMBL)
TryptophanMetabolite27897 (ChEBI) OCR lexicon match: Trp
Xanthurenic acidMetaboliteHMDB00881 (HMDB)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5549"
Personal tools