Molecular Pharmacology, Vol 6, 460-467, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

The Effect of Fluoride on the Reactions of Methanesulfonates with Acetylcholinesterase

¹ Department of Biochemistry, College of Physicians and Surgeons, Columbia University, New York, New York 10023, and Department of Chemistry, University of Colorado, Boulder, Colorado 80302

Methanesulfonates [(3-hydroxyphenyl)trimethylammonium iodide methanesulfonate, 1, 1'-pentamethylenebis(3-hydroxypyridinium iodide) methanesulfonate, and methanesulfonyl fluoride] react with acetylcholinesterase to form an inactive methaneusulfonyl-enzyme derivative analogous to the acetyl-enzyme that is formed during the hydrolysis of esters. The methanesulfonyl-enzyme is desulfonylated by reaction with thiocholine. When the effect of fluoride on these two steps was studied, it was found that fluoride inhibits sulfonylation but does not affect desulfonylation. It was also found that fluoride and a quaternary ammonium ion can bind simultaneously to the enzyme. In one case the binding was independent, in many cases it was partially competitive, in one case it was completely competitive, and in two cases it was cooperative.