Stone T W
Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK.
Toxicon. 2001 Jan;39(1):61-73. doi: 10.1016/s0041-0101(00)00156-2.
In most tissues, including brain, a major proportion of the tryptophan which is not used for protein synthesis is metabolised along the kynurenine pathway. Long regarded as the route by which many mammals generate adequate amounts of the essential co-factor nicotinamide adenine dinucleotide, two components of the pathway are now known to have marked effects on neurones. Quinolinic acid is an agonist at the N-methyl-D-aspartate sensitive subtype of glutamate receptors in the brain, while kynurenic acid is an antagonist and, thus, a potential neuroprotectant. A third kynurenine, 3-hydroxykynurenine, is involved in the generation of free radicals which can also damage neurones. Quinolinic acid is increasingly implicated in neurodegenerative disorders, most especially the AIDS-dementia complex and Huntington's disease, while kynurenic acid has become a standard for the identification of glutamate-releasing synapses, and has been used as the parent for several groups of compounds now being developed as drugs for the treatment of epilepsy and stroke.
在包括大脑在内的大多数组织中，未用于蛋白质合成的色氨酸大部分沿犬尿氨酸途径代谢。长期以来，该途径一直被认为是许多哺乳动物产生足够量必需辅因子烟酰胺腺嘌呤二核苷酸的途径，现在已知该途径的两个成分对神经元有显著影响。喹啉酸是大脑中谷氨酸受体N-甲基-D-天冬氨酸敏感亚型的激动剂，而犬尿喹啉酸是一种拮抗剂，因此是一种潜在的神经保护剂。第三种犬尿氨酸，即3-羟基犬尿氨酸，参与自由基的生成，自由基也会损害神经元。喹啉酸越来越多地与神经退行性疾病有关，尤其是艾滋病痴呆综合征和亨廷顿舞蹈症，而犬尿喹啉酸已成为识别释放谷氨酸的突触的标准物质，并已作为几类正在开发用于治疗癫痫和中风的药物的母体。
