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. 2022 Jan 19;12(1):77–97. doi: 10.5498/wjp.v12.i1.77

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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

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Inflammation shifts kynurenine metabolism pathway towards oxidative stress-associated metabolites. The enzyme indolamine-2,3-dioxygenase (IDO) converts tryptophan to kynurenine. Kynurenine aminotransferase converts kynurenine to kynureninic acid in astrocytes while kynurenine monooxygenase (KMO) metabolizes kynurenine to 3-hyroxykynurenine (3-HK) in microglia. 3-HK is metabolized by kynureninase to 3-hydroxyanthranilic acid and 3-hydroxyanthranilic acid dioxygenase to quinolinic acid. Inflammation up-regulates the enzymes IDO and KMO, resulting in increased levels of KMO-dependent metabolites associated with oxidative stress and depression. IDO: Indolamine-2,3-dioxygenase; KAT: Kynurenine aminotransferase; KMO: Kynurenine monooxygenase; 3-HK: 3-hyroxykynurenine; KYNU: Kynureninase; HAAO: 3-hydroxyanthranilic acid dioxygenase; QA: Quinolinic acid.