Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Trends Pharmacol Sci. 2013 Feb;34(2):136-43. doi: 10.1016/j.tips.2012.09.006. Epub 2012 Nov 1.
The kynurenine pathway of tryptophan metabolism accounts for most of the tryptophan that is not committed to protein synthesis and includes compounds active in the nervous and immune systems. Kynurenine acts on the aryl hydrocarbon receptor, affecting the metabolism of xenobiotics and promoting carcinogenesis. Quinolinic acid is an agonist at N-methyl-D-aspartate receptors (NMDARs), but is also pro-oxidant, has immunomodulatory actions, and promotes the formation of hyperphosphorylated tau proteins. Kynurenic acid blocks NMDARs and α7-homomeric nicotinic cholinoceptors and is also an agonist at the orphan G-protein-coupled receptor GPR35. 3-Hydroxykynurenine and 3-hydroxyanthranilic acid have pronounced redox activity and regulate T cell function. Cinnabarinic acid can activate metabotropic glutamate receptors. This review highlights the increasing range of molecular targets for components of the kynurenine pathway in both the nervous and immune systems in relation to their relevance to disease and drug development.
色氨酸代谢的犬尿氨酸途径负责大部分不用于蛋白质合成的色氨酸，并包括在神经系统和免疫系统中具有活性的化合物。犬尿氨酸作用于芳香烃受体，影响外源性物质的代谢并促进致癌作用。喹啉酸是 N-甲基-D-天冬氨酸受体（NMDAR）的激动剂，但也是促氧化剂，具有免疫调节作用，并促进过度磷酸化的 tau 蛋白的形成。犬尿氨酸酸阻断 NMDAR 和 α7-同型烟碱乙酰胆碱受体，也是孤儿 G 蛋白偶联受体 GPR35 的激动剂。3-羟基犬尿氨酸和 3-羟基邻氨基苯甲酸具有明显的氧化还原活性，并调节 T 细胞功能。肉桂醇酸可以激活代谢型谷氨酸受体。本综述强调了犬尿氨酸途径的成分在神经系统和免疫系统中越来越多的分子靶点，以及它们与疾病和药物开发的相关性。
