犬尿氨酸
芳香烃受体
犬尿氨酸途径
吲哚胺2,3-双加氧酶
巴比妥酸
喹啉酸
生物
邻氨基苯甲酸
癌变
代谢物
分解代谢
生物化学
功能(生物学)
细胞生物学
色氨酸
酶
氨基酸
转录因子
基因
作者
Marta Marszałek‐Grabska,Katarzyna Walczak,Kinga Gaweł,Katarzyna Wicha-Komsta,Sylwia Wnorowska,Artur Wnorowski,Waldemar A. Turski
标识
DOI:10.1016/j.pharmthera.2021.107845
摘要
Kynurenine (KYN), a main metabolite of tryptophan in mammals, is a direct precursor of kynurenic acid, anthranilic acid and 3-hydroxykynurenine (3-HK). Under physiological conditions, KYN is produced endogenously mainly in the liver by tryptophan 2,3-dioxygenase (TDO). Tumorigenesis and inflammatory conditions increase the activity of another KYN synthetizing enzyme, indoleamine 2,3-dioxygenase (IDO). However, knowledge about the exogenous sources and the fate of KYN in mammals is still limited. While most papers deal with the contribution of KYN to pathologies of the central nervous system, its role in the periphery has almost been ignored. KYN is a ligand for the aryl hydrocarbon receptor (AhR). As a receptor for KYN and its downstream metabolites, AhR is involved in several physiological and pathological conditions, including inflammation and carcinogenesis. Recent studies have shown that KYN suppresses immune response and is strongly involved in the process of carcinogenesis and tumour metastasis. Thus, inhibition of activity of the enzymes responsible for KYN synthesis, TDO, IDO or genetic manipulation leading to reduction of KYN synthesis, could be considered as innovative strategies for improving the efficacy of immunotherapy. Surprisingly, however, genetic or pharmacological approaches for reducing tryptophan catabolism to KYN do not necessarily result in decrease of KYN level in the main circulation. This review aims to summarize the current knowledge of KYN fate and function and to emphasize its importance for vital physiological and pathological processes.
科研通智能强力驱动
Strongly Powered by AbleSci AI