Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects
By A. Badawy. International Journal of Tryptophan Research, 2017
1,019 citations recorded by the source corpus.
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 B3 “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.
Subfields: Behavioral Neuroscience, Biological Psychiatry, Psychiatry and Mental health
View Paper: https://www.semanticscholar.org/paper/561104184ed0521c83c50f5ccc16448c8d2130e6
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
- W. El Hage
- Romain Troubat
- V. Camus
- S. Leman
- P. Barone
- C. Belzung
- B. Atanasova
- T. Desmidt
Citations in the corpus
- Physiological roles of tryptophan in teleosts: current knowledge and perspectives for future studies (2019, neutral): “1476 1477 L-tryptophan and B) Main catabolic route for L-tryptophan (kynurenine pathway) 1481 (Badawy, 2017; Falcón et al., 2010; Fernstrom, 2016; Macchiarulo et al., 2009).”
- Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment (2023, neutral): “Anthranilate, a downstream product in the Trp/kynurenine (Kyn) pathway, 51 has been associated with poor prognosis in several diseases including non-small-cell lung and gastric cancer.”
- Neuroinflammation and depression: A review (2020, background): “However, another TRY catabolism pathway involves indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO), which metabolize TRY into KYN (Figure 1) (Badawy, 2017; Guillemin, 2012).”