Comparative Inhibition of Pyridoxal Kinase and Glutamic Acid Decarboxylase by Carbonyl Reagents. ∗

Abstract

Summary

1. Carbonyl reagents such as hydrazine, hydroxylamine and isoniazid inhibit purified preparations of pyridoxal kinase and of glutamic decarboxylase from beef brain, but the kinase is 100 to 1000 times more sensitive. 2. Administration of hydrazine to rats decreases activity of these 2 enzymes in liver and brain; kinase levels are affected more severely. 3. In contrast to their effects in vitro, isoniazid, hydroxylamine, or pyridoxal oxime produced no significant inhibition of kinase or decarboxylase activity in vivo. Pyridoxal oxime appears rapidly catabolized in vivo since its injection results in extensive excretion of 4-pyridoxic acid and its lactone. Unlike free hydroxylamine, injection of pyridoxal oxime does not produce convulsions or extensive methemoglobin formation. 4. Similar administration of pyridoxal azine resulted in rapid and extensive decrease of pyridoxal kinase levels in liver, kidney, and brain. No effects on glutamic acid decarboxylase in brain were observed. 5. These observations demonstrate that individual carbonyl reagents inhibit quite different enzymes in vivo, and indicate that appropriate derivatives of such agents may show enhanced selectivity in their inhibitory actions.