ArticleBiochimica et biophysica acta2016
Tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase 1 make separate, tissue-specific contributions to basal and inflammation-induced kynurenine pathway metabolism in mice.
Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 73 citations in OpenAlex.
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- Shift in the urinary metabolome associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin activation of the hepatic aryl hydrocarbon receptor.Scientific reports · 2025Article
- Tryptophan-induced transcriptomic changes in the European Seabass are highly dependent on neuroendocrine-immune conditions.Scientific reports · 2025Article
- Metabolic Syndrome and Schizophrenia: Adding a Piece to the Interplay Between the Kynurenine Pathway and Inflammation.Metabolites · 2025Review
- Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities.Pharmacological reviews · 2024Review
- A Review of the Evidence for Tryptophan and the Kynurenine Pathway as a Regulator of Stem Cell Niches in Health and Disease.International journal of tryptophan research : IJTR · 2024Review
- Altered Tryptophan-Kynurenine Pathway in Delirium: A Review of the Current Literature.International journal of molecular sciences · 2023Review
- Effects of dietary tryptophan supplementation on rectal temperature, humoral immunity, and cecal microflora composition of heat-stressed broilers.Frontiers in veterinary science · 2023Article
- Kynurenine/Aryl Hydrocarbon Receptor Modulates Mitochondria-Mediated Oxidative Stress and Neuronal Apoptosis in Experimental Intracerebral Hemorrhage.Antioxidants & redox signaling · 2022Article
- IDO/kynurenine pathway in cancer: possible therapeutic approaches.Journal of translational medicine · 2022Review
- Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling.Nature communications · 2022Article
- Targeting Tryptophan Catabolism in Cancer Immunotherapy Era: Challenges and Perspectives.Frontiers in immunology · 2022Review
- A comprehensive analysis of TDO2 expression in immune cells and characterization of immune cell phenotype in TDO2 knockout mice.Transgenic research · 2021Article
- Article
- A single prenatal lipopolysaccharide injection has acute, but not long-lasting, effects on cerebral kynurenine pathway metabolism in mice.The European journal of neuroscience · 2021Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIn mammals, the majority of the essential amino acid tryptophan is degraded via the kynurenine pathway (KP). Several KP metabolites play distinct physiological roles, often linked to immune system functions, and may also be causally involved in human diseases including neurodegenerative disorders, schizophrenia and cancer. Pharmacological manipulation of the KP has therefore become an active area of drug development. To target the pathway effectively, it is important to understand how specific KP enzymes control levels of the bioactive metabolites in vivo.
methodsHere, we conducted a comprehensive biochemical characterization of mice with a targeted deletion of either tryptophan 2,3-dioxygenase (TDO) or indoleamine 2,3-dioxygenase (IDO), the two initial rate-limiting enzymes of the KP. These enzymes catalyze the same reaction, but differ in biochemical characteristics and expression patterns. We measured KP metabolite levels and enzyme activities and expression in several tissues in basal and immune-stimulated conditions. RESULTS AND
conclusionsAlthough our study revealed several unexpected downstream effects on KP metabolism in both knockout mice, the results were essentially consistent with TDO-mediated control of basal KP metabolism and a role of IDO in phenomena involving stimulation of the immune system.
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