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惊厥剂对大鼠脑内丙氨酸转氨酶和天冬氨酸转氨酶活性的影响。

Influence of convulsants on rat brain activities of alanine aminotransferase and aspartate aminotransferase.

作者信息

Netopilová M, Haugvicová R, Kubová H, Drsata J, Mares P

机构信息

Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic.

出版信息

Neurochem Res. 2001 Dec;26(12):1285-91. doi: 10.1023/a:1014386416109.

Abstract

There exist differences between 12-day-old and adult rats in the onset of seizures induced by some inhibitors of glutamate decarboxylase (GAD). The aim of study was to investigate if there are differences between both groups in activities of rat brain alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the enzymes involved in glutamate metabolism, after the administration of 3-mercaptopropionic acid as specific GAD inhibitor or isoniazid as less specific general inhibitor of pyridoxal enzymes. Activities of both aminotransferases in a supernatant 20,000 g of the whole brain (containing predominantly cytosolic isoforms of enzymes) were increased at the beginning of 3-mercaptopropionic acid-induced generalized tonic-clonic seizures. At isoniazid-induced generalized tonic-clonic seizures, a significant increase in both enzyme activities was observed in adult rat brain. In the 12-day-old rat brain, ALT and AST activities reached about 40% and about 50-60% of adult control levels, respectively. In in vitro experiments, no influence of 3-mercaptopropionic acid on transaminase activities was found and an inhibitory effect of isoniazid on the enzymes was confirmed. Increased aminotransferase activities might participate in the enhanced synthesis of excitatory amino acid neurotransmitters in the nervous system, which may take a part in the initiation of epileptic seizures. Alternatively, the increased AST activity may be connected with an increased transport of NADH from the cytosol to mitochondria, while the increased ALT activity would represent the transformation of pyruvate to alanine as a consequence of increased glycolysis.

摘要

12日龄大鼠和成年大鼠在某些谷氨酸脱羧酶(GAD)抑制剂诱发癫痫发作的起始方面存在差异。本研究的目的是探究在给予3-巯基丙酸作为特异性GAD抑制剂或异烟肼作为特异性较低的吡哆醛酶通用抑制剂后,两组大鼠大脑中参与谷氨酸代谢的丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)的活性是否存在差异。在3-巯基丙酸诱发的全身强直阵挛性癫痫发作开始时,全脑20,000 g上清液(主要含有酶的胞质同工型)中两种转氨酶的活性均升高。在异烟肼诱发的全身强直阵挛性癫痫发作时,成年大鼠大脑中两种酶的活性均显著升高。在12日龄大鼠大脑中,ALT和AST的活性分别达到成年对照水平的约40%和约50 - 60%。在体外实验中,未发现3-巯基丙酸对转氨酶活性有影响,并证实了异烟肼对这些酶有抑制作用。转氨酶活性增加可能参与了神经系统中兴奋性氨基酸神经递质合成的增强,这可能在癫痫发作的起始中起作用。或者,AST活性增加可能与NADH从胞质溶胶向线粒体的转运增加有关,而ALT活性增加则可能是糖酵解增加导致丙酮酸转化为丙氨酸的结果。

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