Inactivation of brain glutamate decarboxylase and the effects of adenosine 5'-triphosphate and inorganic phosphate.
The substrate-promoted inactivation of glutamate decarboxylase from hog brain was studied. Inactivation was a slow process that was dependent on the concentration of glutamate. Glutamate-dependent inactivation was not first order but was best described as the sum of two exponential decay processes. At 10 mM glutamate, the half-lives at 30 degrees C were about 6 min for the fast component and 70 min for the slow component. Glutamate-dependent inactivation appeared to be due to the formation of apoenzyme since the rate and extent of inactivation were greatly reduced by the presence of pyridoxal 5'-phosphate (the cofactor, pyridoxal-P). Also, inactivated enzyme could be reactivated by adding pyridoxal-P (Meeley and Martin, 1983). Micromolar concentrations of ATP enhanced glutamate-promoted inactivation in the absence of pyridoxal-P. ATP also enhanced inactivation in the presence of 10 microM pyridoxal-P, but somewhat higher concentrations were required for an equal effect. ATP had little or no direct effect on the enzyme in the absence of glutamate. In the absence of pyridoxal-P, Pi reduced the enhancement of inactivation by 10 microM but not by 750 microM ATP. Glutamate-promoted inactivation, its enhancement by ATP, and the opposition to inactivation by pyridoxal-P and Pi appear to be important in the regulation of glutamate decarboxylase.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D055598:Chemical Phenomena; D002621:Chemistry; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors*; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007700:Kinetics; D010710:Phosphates / Q000494:pharmacology*; D011732:Pyridoxal Phosphate / Q000494:pharmacology; D013552:Swine
D005971:Glutamates; D010710:Phosphates; D018698:Glutamic Acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D002262:Carboxy-Lyases; D005968:Glutamate Decarboxylase