Cho S W, Cho E H, Choi S Y
Department of Biochemistry, College of Medicine, University of Ulsan, Seoul, South Korea.
FEBS Lett. 1998 Apr 17;426(2):196-200. doi: 10.1016/s0014-5793(98)00335-4.
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.
在不同条件下，研究了加巴喷丁对从牛脑匀浆中纯化得到的两种谷氨酸脱氢酶（GDH）同工酶活性的刺激作用。当以NADPH作为辅酶，在2-氧代戊二酸还原胺化方向上研究不同加巴喷丁浓度对GDH活性的影响时，两种同工酶均观察到明显的激活作用；而以NADH作为辅酶时，两种同工酶的激活程度较小。加巴喷丁在谷氨酸氧化脱氨方向上对GDH活性也有刺激作用，但程度远小于还原胺化。两种GDH同工酶对加巴喷丁作用的敏感性存在很大差异。以NADPH作为辅酶时，GDH II的激活作用最大。在约1.5 mM时达到最大刺激的一半。加巴喷丁可缓解GTP对GDH同工酶的抑制作用，并导致在GTP存在下加巴喷丁的表观激活作用增加。发现2-氧代戊二酸会引起高底物抑制，加巴喷丁在0.2 mM NADH存在下可降低底物抑制。由于存在一些GDH活性降低的神经退行性疾病，对该酶活性进行治疗性调节可能具有临床应用价值。
