Inhibition of Brain Glutamate Decarboxylase by Adenosine Triphosphate

ATP acts as an inhibitor of brain glutamate decarboxylase in a water brain tissue extract with low ATPase activity. This inhibition is not caused by competition of ATP with glutamate or pyridoxal‐5‐phosphate.The concentration of ATP, which causes a 50% inhibition of glutamate decarboxylase, [I]50%, depends on the pyridoxal‐5‐phosphate concentration. At 15 μM pyridoxal‐5‐phosphate the [I]50% is 0.3 mM ATP. At 75 μM pyridoxal‐5‐phosphate the [I]50% is 1.3 mM ATP. AT 375 μM pyridoxal‐5‐phosphate glutamate decarboxylase is not inhibited to 50% even with 10 mM ATP.ADP, GTP and UTP are strong inhibitors of glutamate decarboxylase at high concentration. At lower concentrations ATP is the most potent inhibitor. AMP and adenosine do not effect glutamate decarboxylase, nor do they affect the inhibitory action of ATP.Inorganic phosphate in concentrations of 5—40 mM does not influence the activity of glutamate decarboxylase. At the same concentrations Pi diminishes the inhibitory effect of ATP. The [I]50% increases from 0.3 mM ATP (without Pi) to 1.7 mM ATP in the presence of 20 mM Pi.