4.7 Review

Kynurenine-3-monooxygenase (KMO): From its biological functions to therapeutic effect in diseases progression

Journal

JOURNAL OF CELLULAR PHYSIOLOGY
Volume 237, Issue 12, Pages 4339-4355

Publisher

WILEY
DOI: 10.1002/jcp.30876

Keywords

cancer; kynurenine pathway; kynurenine-3-monooxygenase; neurodegenerative diseases; psychosis; small-molecule inhibitors

Funding

  1. National Natural Science Foundation of China

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Kynurenine-3-monooxygenase (KMO) plays a crucial role in the tryptophan metabolism pathway and its dysregulation may be involved in the pathogenesis of various diseases such as neurodegenerative diseases, psychosis, and cancer.
Kynurenine-3-monooxygenase (KMO) is a mitochondrial enzyme involved in the eukaryotic kynurenine pathway (KP), which is the major catabolic route of tryptophan. KMO can convert the substrate kynurenine into the neurotoxin 3-hydroxykynurenine and quinolinic acid, which promote the production of toxic metabolites and formation of free radical in the blood, while decrease the neuroprotective metabolite kynurenic acid. As a result of branch point, KMO is predicted as an attractive drug target for several diseases, especially neurodegenerative diseases, psychosis, and cancer. This review mainly pays attention to KMO structure and the research of mechanisms and functions, with a particular emphasis on the roles of KMO in the pathogenesis of various conditions. Furthermore, we also summarized important KMO inhibitors to supporting their effects on these diseases, indicating the prospect to find novel KMO inhibitors for diseases therapy.

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