Thomas S R, Stocker R
The Biochemistry Group, The Heart Research Institute, Sydney, New South Wales, Australia.
Redox Rep. 1999;4(5):199-220. doi: 10.1179/135100099101534927.
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.
血红素酶吲哚胺2,3-双加氧酶（IDO）可氧化L-色氨酸（Trp）和其他吲哚胺的吡咯部分，是犬尿氨酸（Kyn）途径的起始限速酶。IDO是一种独特的酶，它可以将超氧阴离子自由基（O2*-）既用作底物又用作辅助因子。后一种作用是由于O2*-能够将无活性的铁-IDO还原为活性亚铁形式。一氧化氮（NO）和H2O2会抑制双加氧酶，并且一氧化氮合酶和IDO启动的氨基酸降解途径之间存在各种相互关系。IDO的诱导以及Trp沿Kyn途径的代谢与多种生理和病理生理过程有关，包括抗微生物和抗肿瘤防御、神经病理学、免疫调节和抗氧化活性。抗氧化活性可能源于IDO对O2-的清除以及强效自由基清除剂和Kyn途径代谢产物3-羟基邻氨基苯甲酸和3-羟基犬尿氨酸的形成。在某些条件下，这些氨基酚和其他Kyn途径代谢产物可能会表现出促氧化活性。本文综述了相关研究结果，表明氧化还原反应参与了Kyn途径中IDO和Trp代谢的调节，并且还参与了Kyn途径代谢产物所表现出的生物活性。
