Inhibition of Acetylcholinesterase Activity by Aromatic Chelating Agents

1 Form B of acetylcholinesterase from toluene‐treated electric organs of the electric eel was inhibited in a non‐competitive manner by chelating agents such as 1,10‐phenanthroline, 8‐hydroxyquinoline, 2,2′‐dipyridyl and salicylic aldehyde. The apparent inhibition constants ranged between 1.3 mM and 4.8 mM. Secondary plots revealed hyperbolic inhibition for 1,10‐phenanthroline, slope‐parabolic‐intercept‐linear inhibition for 8‐hydroxyquinoline, slope‐linear‐intercept‐hyperbolic inhibition for 2,2′‐dipyridyl and a linear inhibition pattern for salicylic aldehyde. 2 The direct participation of metal cations in the catalytic process could be ruled out on the following basis: the inhibition of the enzyme by chelating agents was rapid and reversible; it did not show any time‐dependent irreversible inactivation. Excess metal did not reverse the inhibition: metal · chelate complexes inhibited the enzyme similarly or even stronger as did the complexing agents by themselves. No inhibition, even at concentrations up to 0.1 M was observed with EDTA. 3 With 8‐hydroxyquinoline at pH 6.0 non‐linear double‐reciprocal plots were observed. The Hill coefficients were 1.01, 1.20, 1.30 and 1.32 for 0, 0.75, 1.50 and 3.00 mM 8‐hydroxyquinoline. 4 The inhibitory effects of these compounds were explained in terms of hydrophobic adsorption of aromatic nuclei at the active center and in terms of structural similarities to the substrate. The type of inhibition observed by these compounds is indicative of co‐operative binding of these ligands to acetylcholinesterase.