TY - JOUR T1 - The Effect of Fluoride on the Reactions of Methanesulfonates with Acetylcholinesterase JF - Molecular Pharmacology JO - Mol Pharmacol SP - 460 LP - 467 VL - 6 IS - 5 AU - CAROL M. GREENSPAN AU - IRWIN B. WILSON Y1 - 1970/09/01 UR - http://molpharm.aspetjournals.org/content/6/5/460.abstract N2 - 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. ER -