Action of Fluoride on Cholinesterase. I. On the Mechanism of Inhibition.

Abstract

The effect of sodium fluoride upon acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) has been studied. The compound inhibits both enzymes reversibly, the type and degree of inhibition depending upon the substrate used. When the latter is acetylcholine, mixed inhibition of AChE is found, while the inhibition of AChE with N-methylaminoethyl acetate as substrate is noncompetitive. Some kinetic constants are calculated. The inhibition of crude plasma BuCh produced by NaF and that produced by excess of the substrate benzoylcholine interfere with each other, the total inhibition being less than that produced by F- alone. Inhibition at pH 7.4, due to the simultaneous presence of trimethylammonium bromide and fluoride, is less than additive. The NaF induced inhibition of both AChE and BuChE increases when the temperature is lowered and also when the pH is lowered. Some possible mechanisms of inhibition are discussed. It is suggested that both the F- ion, HF and the HF2- ion are inhibitors of cholinesterases and that acylation and possibly also deacylation of the enzymes may be blocked.