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

Abstract

The recombinant forms of the two human isozymes of glutamate decarboxylase, GAD65 and GAD67, are potently and reversibly inhibited by molecular oxygen (Ki = 0.46 and 0.29 mM, respectively). Inhibition of the vesicle-associated glutamate decarboxylase (GAD65) by molecular oxygen is likely to result in incomplete filling of synaptic vesicles with gamma-aminobutyric acid (GABA) and may be a contributing factor in the genesis of oxygen-induced seizures. Under anaerobic conditions, nitric oxide inhibits both GAD65 and GAD67 with comparable potency to molecular oxygen (Ki = 0.5 mM). Two forms of porcine cysteine sulfinic acid decarboxylase (CSADI and CSADII) are also sensitive to inhibition by molecular oxygen (Ki = 0.30 and 0.22 mM, respectively) and nitric oxide (Ki = 0.3 and 0.2 mM, respectively). Similar inhibition of glutamate decarboxylase and cysteine sulfinic acid decarboxylase by two different radical-containing compounds (O2 and NO) is consistent with the notion that these reactions proceed via radical mechanisms.

• Authors: K Davis, T Foos, J Y Wu, J V Schloss
• Journal: Journal of biomedical science (J Biomed Sci) 2001 Jul-Aug Vol. 8 Issue 4 Pg. 359-64 ISSN: 1021-7770 [Print] England
• PMID: 11455199 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright 2001 National Science Council, ROC and S. Karger AG, Basel

Chemical References

• Recombinant Proteins
• Nitric Oxide
• Carboxy-Lyases
• Glutamate Decarboxylase
• sulfoalanine decarboxylase
• Oxygen

Topics

• Animals
• Carboxy-Lyases (antagonists & inhibitors)
• Glutamate Decarboxylase (antagonists & inhibitors)
• Humans
• Nitric Oxide (pharmacology)
• Oxygen (adverse effects, pharmacology)
• Recombinant Proteins (antagonists & inhibitors)
• Seizures (chemically induced)
• Swine