Inhibition of Drosophila acetylcholinesterase by 7-(methylethoxyphosphlinyloxy)1-methyl-quinolinium iodide

The kinetic behaviour of Drosophila melanogaster acetylcholinesterase towar d its substrate shows, in comparison with classic Michaelis-Menten kinetics , an apparent homotropic cooperative double activation-inhibition pattern. In order to construct an appropriate kinetic model and obtain further infor mation on the mechanism of the catalytic action of this enzyme, the hydroly sis of acetylthiocholine in the absence and presence of different concentra tions of synthetic quaternary methylphosphonate, 7-(methylethoxyphosphinylo xy)1-methyl-quinolinium iodide (MEPQ), was followed on a stopped-flow appar atus. The reaction at low substrate concentrations was followed until the c hange of the absorbance became negligible and at high concentrations only i nitial parts were recorded. A simultaneous analysis of the progress curves using numerical integration showed that the powerful organophosphonate inhi bitor binds and compete with the substrate for the same binding sites. The results are also in accordance with the hypothesis that virtually every sub strate or quasi-substrate molecule that enters into the gorge of active sit e is hydrolysed. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved .