M-(N,N,N-TRIMETHYLAMMONIO)TRIFLUOROACETOPHENONE - A FEMTOMOLAR INHIBITOR OF ACETYLCHOLINESTERASE

m-(N,N,N-Trimethylammonio)trifluoroacetophenone is a potent, reversibl e, time-dependent inhibitor of acetylcholinesterases. The respective s econd-order rate constants (k(on)) for binding of the ketone to enzyme s from Electrophorus electricus and Torpedo californica are (1.2 +/- 0 .2) X 10(5) and (1.0 + 0.2) X 10(5) M-1 s-1, while the corresponding d issociation rate constants (k(off)) are (1.0 +/- 0.2) X 10(-5) and (1. 0 +/- 0.3) X 10(-4) s-1. Therefore, the apparent dissociation constant s of the enzyme-inhibitor complexes (K(i)app = k(off)/k(on)) are 80 +/ - 20 pM and 1.0 +/- 0.3 nM, respectively. Because the free ketone is t he form that inhibits acetylcholinesterases, intrinsic dissociation co nstants were calculated by correcting the K(i)app values for the exten t of hydration of the inhibitor. The resulting K(i) values are 1.3 and 15 fM for inhibitions of E. electricus and T. californica acetylcholi nesterases, respectively.