Redox reactions related to indoleamine 2,3-dioxygenase and tryptophan metabolism along the kynurenine pathway
Open Access
- 1 October 1999
- journal article
- review article
- Published by Taylor & Francis Ltd in Redox Report
- Vol. 4 (5), 199-220
- https://doi.org/10.1179/135100099101534927
Abstract
The heme enzyme indoleamine 2,3-dioxygenase (IDO) oxidizes the pyrrole moiety of L-tryptophan (Trp) and other indoleamines and represents the initial and rate-limiting enzyme of the kynurenine (Kyn) pathway. IDO is a unique enzyme in that it can utilize superoxide anion radical (O2*- ) as both a substrate and a co-factor. The latter role is due to the ability of O2*- to reduce inactive ferric-IDO to the active ferrous form. Nitrogen monoxide (*NO) and H2O2 inhibit the dioxygenase and various inter-relationships between the nitric oxide synthase- and IDO-initiated amino acid degradative pathways exist. Induction of IDO and metabolism of Trp along the Kyn pathway is implicated in a variety of physiological and pathophysiological processes, including anti-microbial and anti-tumor defense, neuropathology, immunoregulation and antioxidant activity. Antioxidant activity may arise from O2*- scavenging by IDO and formation of the potent radical scavengers and Kyn pathway metabolites, 3-hydroxyanthranilic acid and 3-hydroxykynurenine. Under certain conditions, these aminophenols and other Kyn pathway metabolites may exhibit pro-oxidant activities. This article reviews findings indicating that redox reactions are involved in the regulation of IDO and Trp metabolism along the Kyn pathway and also participate in the biological activities exhibited by Kyn pathway metabolites.Keywords
This publication has 237 references indexed in Scilit:
- Neopterin Derivatives Modulate the Nitration of Tyrosine by PeroxynitriteBiochemical and Biophysical Research Communications, 1998
- Gene structure of human indoleamine 2,3-dioxygenaseBiochemical and Biophysical Research Communications, 1992
- Evaluation of nitrite production by human monocyte-derived macrophagesBiochemical and Biophysical Research Communications, 1992
- Release of nitric oxide from human vascular smooth muscle cellsBiochemical and Biophysical Research Communications, 1991
- The role of hydrogen peroxide in the in vitro cytotoxicity of 3-hydroxykynurenineNeurochemical Research, 1990
- Spectroscopic and equilibrium studies of ligand and organic substrate binding to indolamine 2,3-dioxygenaseBiochemistry, 1990
- The actions of interferon and antiinflammatory agents on induction of indoleamine 2,3-dioxygenase in human peripheral blood monocytesBiochemical and Biophysical Research Communications, 1987
- Cofactor activity of dihydroflavin mononucleotide and tetrahydrobiopterin for murine epididymal indoleamine 2,3-dioxygenaseBiochemical and Biophysical Research Communications, 1986
- Kynurenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acidNeuroscience Letters, 1984
- Enhanced xanthine oxidase activity in mice treated with interferon and interferon inducersBiochemical and Biophysical Research Communications, 1984