Hartai Zsuzsanna, Klivenyi Peter, Janaky Tamas, Penke Botond, Dux Laszlo, Vecsei Laszlo
Department of Neurology, University of Szeged, Szeged, Hungary.
Med Chem. 2007 May;3(3):285-8. doi: 10.2174/157340607780620707.
Substantial evidence indicates that neuroactive kynurenine metabolites play a role in the normal physiology of the human brain, and are involved in the pathology of neurodegenerative disorders such as Parkinson's disease and Huntington's disease. A side-arm product of the pathway, kynurenic acid (KYNA), which is synthesized by the irreversible transamination of kynurenine (KYN) by kynurenine aminotransferases (KAT I and KAT II), is an excitatory amino acid receptor antagonist. In the present study, we measured the level of KYNA and the activities of the biosynthetic enzyme isoforms KAT I and KAT II in the plasma and in the erythrocytes (RBCs) of patients with cervical dystonia or blepharospasm and in age-matched controls. The KAT I and KAT II activities were significantly lower in the plasma of the patients in both subgroups. In the RBCs, only the KAT I activity was elevated significantly. The KYNA concentration was unchanged in both type of patients. These data support the contribution of an altered kynurenine metabolism to the pathogenesis of focal dystonia.
大量证据表明，具有神经活性的犬尿氨酸代谢产物在人类大脑的正常生理过程中发挥作用，并参与帕金森病和亨廷顿病等神经退行性疾病的病理过程。该代谢途径的一个旁支产物犬尿喹啉酸（KYNA），由犬尿氨酸转氨酶（KAT I和KAT II）将犬尿氨酸（KYN）不可逆转氨合成，是一种兴奋性氨基酸受体拮抗剂。在本研究中，我们测量了颈部肌张力障碍或眼睑痉挛患者以及年龄匹配对照组的血浆和红细胞（RBC）中KYNA的水平以及生物合成酶同工型KAT I和KAT II的活性。两个亚组患者的血浆中KAT I和KAT II活性均显著降低。在红细胞中，只有KAT I活性显著升高。两种类型患者的KYNA浓度均未改变。这些数据支持犬尿氨酸代谢改变对焦距性肌张力障碍发病机制的作用。
