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Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects
Open accessAbstract
Regulatory and functional aspects of the kynurenine (K) pathway (KP) of tryptophan (Trp) degradation are reviewed. The KP accounts for ~95% of dietary Trp degradation, of which 90% is attributed to the hepatic KP. During immune activation, the minor extrahepatic KP plays a more active role. The KP is rate-limited by its first enzyme, Trp 2,3-dioxygenase (TDO), in liver and indoleamine 2,3-dioxygenase (IDO) elsewhere. TDO is regulated by glucocorticoid induction, substrate activation and stabilization by Trp, cofactor activation by heme, and end-product inhibition by reduced nicotinamide adenine dinucleotide (phosphate). IDO is regulated by IFN-γ and other cytokines and by nitric oxide. The KP disposes of excess Trp, controls hepatic heme synthesis and Trp availability for cerebral serotonin synthesis, and produces immunoregulatory and neuroactive metabolites, the B 3 “vitamin” nicotinic acid, and oxidized nicotinamide adenine dinucleotide. Various KP enzymes are undermined in disease and are targeted for therapy of conditions ranging from immunological, neurological, and neurodegenerative conditions to cancer.
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“The Trp-Kyn-AhR pathway, in which the essential amino acid tryptophan is converted to Kyn and other secondary metabolites, is the primary route of tryptophan catabolism (19).”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [19]
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Metadata
- Authors
- Badawy, A. A.-B.
- Affiliations
- Cardiff Metropolitan University (GB)
- Corresponding author
- Badawy, Abdulla A-B
- ORCID
- Badawy, Abdulla A-B
- Venue
- International Journal of Tryptophan Research
- Publisher
- SAGE Publications
- Published
- 2017-01-01
- Volume
- 10
- Pages
- 1178646917691938-1178646917691938
- ISSN
- 1178-6469 (ISSN-L)
- PMC
- PMC5398323
- OpenAlex
- W2598111690
- Cited by
- 1,158
- References
- 203
- Citations by year
- 2026: 147 · 2025: 179 · 2024: 137 · 2023: 153 · 2022: 148 · 2021: 148 · 2020: 119 · 2019: 75 · 2018: 45 · 2017: 7
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- International Journal of Tryptophan Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
- Keywords
- kynurenine pathway, tryptophan metabolism, tryptophan 2,3-dioxygenase, indoleamine 2,3-dioxygenase, glucocorticoid regulation, nitric oxide, NADP+ inhibition, heme biosynthesis, serotonin synthesis, NAD+, immune regulation, neuroactive metabolites, neurodegenerative diseases, cancer therapy
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