BMB Reports
- 제34권3호
- /
- Pages.268-273
- /
- 2001
- /
- 1976-670X(eISSN)
Inactivation of Brain Glutamate Dehydrogenase Isoproteins by MDL 29951
- Lee, Eun-Young (Department of Biochemistry, University of Ulsan College of Medicine) ;
- Yoon, Hye-Young (Department of Biochemistry, University of Ulsan College of Medicine) ;
-
Kim, Tae-Ue
(Department of Medical Technology, College of Health Science, Yonsei University) ;
- Choi, Soo-Young (Department of Genetic Engineering, Division of Life Sciences) ;
-
Won, Moo-Ho
(Department of Anatomy, College of Medicine, Hallym University) ;
- Cho, Sung-Woo (Department of Biochemistry, University of Ulsan College of Medicine)
- 투고 : 2001.01.29
- 심사 : 2001.02.09
- 발행 : 2001.05.31
초록
In addition to the recognition site for glutamate, the N-methyl-D-aspartate (NMDA)-preferring glutamate receptor subtype shows a binding site for glycine. In this paper, we present the effects of 3-(4,6-dichloro-2-carboxymethylamino-5,7-dichloroquinoline-2-carboxylic acid (MDL 29951), a potent inhibitor of glycine binding to the NMDA receptor, on glutamate dehydrogenase (GDH) from bovine brains. The incubation of GDH isoproteins from bovine brains with MDL 29951 resulted in a dose-dependent loss of enzyme activity Separately or together, 2-oxoglutarate and NADH did not give an efficient protection against the inhibition, indicating that GDH isoproteins saturated with NADH or 2-oxoglutarate are still open to attack by MDL 29951. MDL 29951 was an uncompetitive inhibitor with respect to both 2-oxoglutarate and NADH for GDH isoproteins. These results suggest that the binding site of MDL 29951 is not directly located at the catalytic site, and the inhibition of GDH isoproteins by MDL 29951 is probably due to a steric hindrance, or a conformational change altered upon the interaction of the enzyme with its inhibitor. The inhibitory effects of MDL 29951 on GDH isoproteins were significantly diminished in the presence of ADP. GDH I reacted more sensitively with ADP than GDH II on the inhibition by MDL 29951. Our results suggest a possibility that the two types of GDHs are differently regulated by MDL 29951, depending on the physiological concentrations of ADP.