Activation of two types of brain glutamate dehydrogenase isoproteins by gabapentin

FEBS Letters

Cho, Eun Hee¹  Choi, Soo Young³  Cho, Sung-Woo² 

[1] Department of Science Education, College of Education, Chosun University, Kwangju 501-759, South Korea;Department of Biochemistry, College of Medicine, University of Ulsan, 388-1 Poongnap-dong, Songpa-Ku, Seoul 138-736, South Korea;Department of Genetic Engineering, College of Natural Sciences, Hallym University, Chunchon 200-702, South Korea

关键词: Glutamate dehydrogenase isoprotein;    Gabapentin;    Enzyme activation;    Neurodegenerative disorder;    GDH;    glutamate dehydrogenase;   

DOI  :  10.1016/S0014-5793(98)00335-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The stimulatory effects of gabapentin on the activities of two types of glutamate dehydrogenase (GDH) isoproteins homogeneously purified from bovine brain have been studied at various conditions. When the effects of different gabapentin concentrations on GDH activities were studied in the direction of reductive amination of 2-oxoglutarate with NADPH as a coenzyme, a marked activation was observed for both isoproteins, whereas both isoproteins showed activation to a lesser extent with NADH as a coenzyme. Stimulatory effects of gabapentin on GDH activities in the direction of the oxidative deamination of glutamate were also observed, but to a much lesser extent than reductive amination. There were big differences between the two GDH isoproteins in their sensitivity to the action of gabapentin. The largest activation was observed with GDH II when NADPH was used as a coenzyme. Half-maximal stimulation was reached at around 1.5 mM. Gabapentin relieved the inhibition of GDH isoproteins by GTP and this resulted in an increase in the apparent activation by gabapentin in the presence of GTP. 2-Oxoglutarate was found to give rise to high substrate inhibition and gabapentin reduced the substrate inhibition in the presence of 0.2 mM NADH. Since there are neurodegenerative disorders in which GDH activity is decreased, the therapeutic modulation of the activity of this enzyme may be clinically useful.

【 授权许可】

Unknown