PT - JOURNAL ARTICLE AU - MIRIAM ZAHAVI AU - A. S. TAHORI AU - FANICA KLIMER TI - Insensitivity of Acetylcholinesterases to Organophosphorus Compounds as Related to Size of Esteratic Site DP - 1971 Nov 01 TA - Molecular Pharmacology PG - 611--619 VI - 7 IP - 6 4099 - http://molpharm.aspetjournals.org/content/7/6/611.short 4100 - http://molpharm.aspetjournals.org/content/7/6/611.full SO - Mol Pharmacol1971 Nov 01; 7 AB - The activity patterns of sensitive and organophosphorus-insensitive acetylcholinesterases of mites were tested with a homologous series of three acylthiocholines. The activities of organophosphorus-sensitive enzymes from two mite strains were higher with propionylthiocholine than with acetylthiocholine, and decreased sharply with butyrylthiocholine. On the other hand, the organophosphorus-insensitive acetylcholinesterases from three resistant mite strains displayed decreasing activity in the following order: acetylthiocholine > propionylthiocholine > butyrylthiocholine. An essentially similar difference between sensitive and insensitive acetylcholinesterases was also observed when 1/Km or maximal velocities were determined for the three acylthiocholine substrates. Consequently, with propionylthiocholine as substrate, the activities, 1/Km values, and maximal velocities of organophosphorus insensitive enzymes were much lower than those of organophosphorus-sensitive acetylcholinesterases. In view of these results and of the considerably lower extent of inhibition of mite acetylcholinesterase by the O,O-diethyl analogue of malaoxon, as compared to that by malaoxon (S-(1,2-dicarbethoxymethyl O,O-dimethyl)phosphorothioate) itself, it is suggested that the esteratic site of the organophosphorus-sensitive mite enzyme is wide enough to accommodate the O,O-dimethylphosphoryl residue of malaoxon but not an O,O-diethylphosphoryl residue. On the other hand, the esteratic site of organophosphorus-insensitive acetylcholinesterase is not wide enough to accommodate even an O,O-dimethylphosphoryl residue. The pattern of activities of organophosphorus-sensitive acetylcholinesterases from aphids, roaches, and Mediterranean fruit flies, and of organophosphorus-insensitive acetylcholinesterase from toad brains, was also tested with the three acylthiocholines. With the sensitive enzymes only the pattern of 1/Km values was similar to that of the sensitive enzyme of mites for the three acylthiocholines tested. ACKNOWLEDGMENTS The assistance of Mr. I. Rogosick in rearing the mites and aphids and the gifts of the D- and L-stereoisomers of the O,O-diethyl analogue of malaoxon by Dr. W. C. Dauterman, and of purified malaoxon by American Cyanamid Company, are gratefully acknowledged. Figure 1 was photographed by Dr. A. Vincze.