title: Redox reactions related to indoleamine 2,3-dioxygenase and tryptophan metabolism along the kynurenine pathway.
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.
authors.affiliation: The Biochemistry Group, The Heart Research Institute, Sydney, New South Wales, Australia. s.thomas@hri.org.au
authors.forename: S R
authors.initials: SR
authors.lastname: Thomas
authors.forename: R
authors.initials: R
authors.lastname: Stocker
mesh_terms: D000818:Animals; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine / Q000378:metabolism*; D010084:Oxidation-Reduction; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan; D014366:Tryptophan Oxygenase