Inhibition of acetylcholinesterase from different species by organophosphorus compounds, carbamates and methylsulphonylfluoride

Abstract

1. 1. Frog brain acetylcholinesterase (AChE) was more resistant to inhibition by organophosphorus compounds than chicken and rat brain AChE. The differences in inhibition rates were 2 times for soman, 10 times for sarin, tabun and Tx-60, 100 times for DFP, dimethylphosphorylfluoride and paraoxon and 1000 times for diethylphosphorylfluoride. 2. 2. Physostigmine and neostigmine inhibited chicken and rat brain AChE about 100 times faster than frog brain AChE. 3. 3. Chicken and rat brain AChE were inhibited only slightly faster by methylsulphonylfluoride than the frog brain AChE. The inhibition was accelerated by tetraethylammonium ions and retarded by tensilon in all cases. 4. 4. Tetraethylammonium ions, however, slightly retarded the inhibition rate of chicken and rat brain AChE by dimethylphosphorylfluoride. No significant effect was observed for the frog brain AChE. 5. 5. The species differences in inhibition rates were probably not due to differences in phosphorylation rates or conformational changes, but rather to the steric arrangement in the active site of the enzyme molecules.