title: 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.affiliation: Department of Medicinal Chemistry, University of Kansas, Lawrence, Kans, USA.
authors.forename: K
authors.initials: K
authors.lastname: Davis
authors.forename: T
authors.initials: T
authors.lastname: Foos
authors.forename: J Y
authors.initials: JY
authors.lastname: Wu
authors.forename: J V
authors.initials: JV
authors.lastname: Schloss
mesh_terms: D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors*; D006801:Humans; D009569:Nitric Oxide / Q000494:pharmacology*; D010100:Oxygen / Q000009:adverse effects* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced*; D013552:Swine
chemical_list: D011994:Recombinant Proteins; D009569:Nitric Oxide; D002262:Carboxy-Lyases; D005968:Glutamate Decarboxylase; C019972:sulfoalanine decarboxylase; D010100:Oxygen