ArticleThe Journal of biological chemistry2013
Human indoleamine 2,3-dioxygenase is a catalyst of physiological heme peroxidase reactions: implications for the inhibition of dioxygenase activity by hydrogen peroxide.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Pooled it
- Engineered indoleamine 2,3-dioxygenase variant: Oxidative activation of prodrug indole-3-acetic acid against cancer cells for targeted therapy.Molecular therapy. Oncology · 2026Article
- Engineering an indoleamine 2,3-dioxygenase immunotherapyMolecular systems design & engineering · 2025Article
- Gasdermin D promotes development of intestinal tumors through regulating IL-1β release and gut microbiota composition.Cell communication and signaling : CCS · 2024Article
- Alcohol extract ofBiomedical reports · 2024Article
- The development of an ingestible biosensor for the characterization of gut metabolites related to major depressive disorder: hypothesis and theory.Frontiers in systems biology · 2023Article
- IDO1 Modulates the Sensitivity of Epithelial Ovarian Cancer Cells to Cisplatin through ROS/p53-Dependent Apoptosis.International journal of molecular sciences · 2022Article
- Indoleamine 2,3-dioxygenase 1 (IDO1): an up-to-date overview of an eclectic immunoregulatory enzyme.The FEBS journal · 2022Review
- Biological Mechanisms ofAntioxidants (Basel, Switzerland) · 2021Review
- Targeting Dietary and Microbial Tryptophan-Indole Metabolism as Therapeutic Approaches to Colon Cancer.Nutrients · 2021Review
- Gut Biofactory-Neurocompetent Metabolites within the Gastrointestinal Tract. A Scoping Review.Nutrients · 2020Article
- Tat-indoleamine 2,3-dioxygenase 1 elicits neuroprotective effects on ischemic injury.BMB reports · 2020Article
- Tryptophan Metabolites Along the Microbiota-Gut-Brain Axis: An Interkingdom Communication System Influencing the Gut in Health and Disease.International journal of tryptophan research : IJTR · 2020Review
- Microbiota Alterations in Alzheimer's Disease: Involvement of the Kynurenine Pathway and Inflammation.Neurotoxicity research · 2019Review
- Article
- Targeting regulation of tryptophan metabolism for colorectal cancer therapy: a systematic review.RSC advances · 2019Review
- Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential.Frontiers in neuroscience · 2019Review
- Microorganisms, Tryptophan Metabolism, and Kynurenine Pathway: A Complex Interconnected Loop Influencing Human Health Status.International journal of tryptophan research : IJTR · 2019Review
- Oxygen Activation and Radical Transformations in Heme Proteins and Metalloporphyrins.Chemical reviews · 2018Review
- Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism.Frontiers in cellular and infection microbiology · 2018Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The heme enzyme indoleamine 2,3-dioxygenase (IDO) is a key regulator of immune responses through catalyzing l-tryptophan (l-Trp) oxidation. Here, we show that hydrogen peroxide (H(2)O(2)) activates the peroxidase function of IDO to induce protein oxidation and inhibit dioxygenase activity. Exposure of IDO-expressing cells or recombinant human IDO (rIDO) to H(2)O(2) inhibited dioxygenase activity in a manner abrogated by l-Trp. Dioxygenase inhibition correlated with IDO-catalyzed H(2)O(2) consumption, compound I-mediated formation of protein-centered radicals, altered protein secondary structure, and opening of the distal heme pocket to promote nonproductive substrate binding; these changes were inhibited by l-Trp, the heme ligand cyanide, or free radical scavengers. Protection by l-Trp coincided with its oxidation into oxindolylalanine and kynurenine and the formation of a compound II-type ferryl-oxo heme. Physiological peroxidase substrates, ascorbate or tyrosine, enhanced rIDO-mediated H(2)O(2) consumption and attenuated H(2)O(2)-induced protein oxidation and dioxygenase inhibition. In the presence of H(2)O(2), rIDO catalytically consumed nitric oxide (NO) and utilized nitrite to promote 3-nitrotyrosine formation on IDO. The promotion of H(2)O(2) consumption by peroxidase substrates, NO consumption, and IDO nitration was inhibited by l-Trp. This study identifies IDO as a heme peroxidase that, in the absence of substrates, self-inactivates dioxygenase activity via compound I-initiated protein oxidation. l-Trp protects against dioxygenase inactivation by reacting with compound I and retarding compound II reduction to suppress peroxidase turnover. Peroxidase-mediated dioxygenase inactivation, NO consumption, or protein nitration may modulate the biological actions of IDO expressed in inflammatory tissues where the levels of H(2)O(2) and NO are elevated and l-Trp is low.
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Registered trials
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