Oxygen-induced seizures and inhibition of human glutamate decarboxylase and porcine cysteine sulfinic acid decarboxylase by oxygen and nitric oxide

The recombinant forms of the two human isozymes of glutamate decarboxylase, GAD65 and GAD67, are potently and reversibly inhibited by molecular oxygen (K-i = 0.46 and 0.29 mM, respectively). inhibition of the vesicle-associat ed glutamate decarboxylase (GAD65) by molecular oxygen is likely to result in incomplete filling of synaptic vesicles with gamma -aminobutyric acid (G ABA) and may be a contributing factor in the genesis of oxygen-induced seiz ures. Under anaerobic conditions, nitric oxide inhibits both GAD65 and GAD6 7 with comparable potency to molecular oxygen (K-i = 0.5 mM). Two forms of porcine cysteine sulfinic acid decarboxylase (CSADI and CSADII) are also se nsitive to inhibition by molecular oxygen (Ki = 0.30 and 0.22 mM, respectiv ely) and nitric oxide (K-i = 0.3 and 0.2 mM respectively). Similar inhibiti on of glutamate decarboxylase and cysteine sulfinic acid decarboxylase by t wo different radical-containing compounds (O-2 and NO) is consistent with t he notion that these reactions proceed via radical mechanisms. Copyright (C ) 2001 National Science Council, ROC and S. Karger AG, Basel.