Cited by 1,158Tryptophan and brain disordersAmino Acid Enzymes and MetabolismMicrobial Natural Products and Biosynthesis

Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects

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Badawy, Abdulla A-B·2017·International Journal of Tryptophan Research

Abstract

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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  1. [50]Shibata K Hayakawa T Iwai K Tissue distribution of the enzymes concerned with the biosynthesis of NAD in rats. Agr Biol Chem. 1986; 50: 3037– 3041.
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Authors
Badawy, A. A.-B.
Affiliations
Cardiff Metropolitan University (GB)
Corresponding author
Badawy, Abdulla A-B
Venue
International Journal of Tryptophan Research
Published
2017-01-01
Volume
10
Pages
1178646917691938-1178646917691938
ISSN
1178-6469 (ISSN-L)
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
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
  • Health Sciences › Medicine › Pharmacology › 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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