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dc.contributor.authorStavrum, Anne-Kristin
dc.contributor.authorHeiland, Ines
dc.contributor.authorSchuster, Stefan
dc.contributor.authorPuntervoll, Pål
dc.contributor.authorZiegler, Mathias
dc.date.accessioned2014-01-08T10:30:00Z
dc.date.available2014-10-15T05:50:03Z
dc.date.issued2013
dc.description.abstractTryptophan is utilized in various metabolic routes including protein synthesis, serotonin, and melatonin synthesis and the kynurenine pathway. Perturbations in these pathways have been associated with neurodegenerative diseases and cancer. Here we present a comprehensive kinetic model of the complex network of human tryptophan metabolism based upon existing kinetic data for all enzymatic conversions and transporters. By integrating tissue-specific expression data, modeling tryptophan metabolism in liver and brain returned intermediate metabolite concentrations in the physiological range. Sensitivity and metabolic control analyses identified expected key enzymes to govern fluxes in the branches of the network. Combining tissue-specific models revealed a considerable impact of the kynurenine pathway in liver on the concentrations of neuroactive derivatives in the brain. Moreover, using expression data from a cancer study predicted metabolite changes that resembled the experimental observations. We conclude that the combination of the kinetic model with expression data represents a powerful diagnostic tool to predict alterations in tryptophan metabolism. The model is readily scalable to include more tissues, thereby enabling assessment of organismal tryptophan metabolism in health and diseaseen
dc.identifier.citationJournal of Biological Chemistry 288(2013) nr. 48 s. 34555-34566en
dc.identifier.cristinIDFRIDAID 1073834
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M113.474908
dc.identifier.issn0021-9258
dc.identifier.urihttps://hdl.handle.net/10037/5710
dc.identifier.urnURN:NBN:no-uit_munin_5410
dc.language.isoengen
dc.rights.accessRightsopenAccess
dc.subjectVDP::Mathematics and natural science: 400::Information and communication science: 420::Mathematical modeling and numerical methods: 427en
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Informasjons- og kommunikasjonsvitenskap: 420::Matematisk modellering og numeriske metoder: 427en
dc.titleModel of Tryptophan Metabolism, Readily Scalable Using Tissue-specific Gene Expression Dataen
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


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