Chen Yanmei, Zhang Jiahui, Yang Yueying, Xiang Ke, Li Hua, Sun Dejuan, Chen Lixia
Key Laboratory of Structure-Based Drug Design & Discovery, Wuya College of Innovation, School of Traditional Chinese Materia Medica, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, China.
College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
J Cell Physiol. 2022 Dec;237(12):4339-4355. doi: 10.1002/jcp.30876. Epub 2022 Sep 11.
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.
犬尿氨酸-3-单加氧酶(KMO)是一种参与真核生物犬尿氨酸途径(KP)的线粒体酶,而犬尿氨酸途径是色氨酸的主要分解代谢途径。KMO可将底物犬尿氨酸转化为神经毒素3-羟基犬尿氨酸和喹啉酸,这会促进血液中有毒代谢物的产生和自由基的形成,同时减少具有神经保护作用的代谢物犬尿酸。作为分支点,KMO被认为是几种疾病,尤其是神经退行性疾病、精神病和癌症的有吸引力的药物靶点。本综述主要关注KMO的结构以及机制和功能的研究,特别强调KMO在各种病症发病机制中的作用。此外,我们还总结了重要的KMO抑制剂,以支持它们对这些疾病的作用,表明寻找新型KMO抑制剂用于疾病治疗的前景。