Effect of tetramethylammonium, choline and edrophonium on insect acetylcholinesterase: test of a kinetic model

Cholinesterases display a non-Michaelian behaviour with respect to substrat e,concentration. With the insect enzyme, there is an activation at low subs trate concentrations and an inhibition at high concentrations. Previous stu dies allow us to propose a kinetic model involving a secondary non-producti ve binding site for the substrate. Unexpectedly, this secondary site has a very high affinity for the substrate when the enzyme is free. On the contra ry, when the catalytic site of the enzyme is occupied a strong decrease of this affinity was observed. Moreover, a substrate molecule bound to the per ipheral site results in a global decrease of the acylation and/or the deacy lation step. Kinetic studies with three reversible inhibitors, tetramethyla mmonium, edrophonium and choline supported the kinetic model and enable its further refinement. (C) 1999 Elsevier Science Ireland Ltd. All rights rese rved.