Kinetics of inhibition of acetylcholinesterase by spin labeled acetylcholine analogs.
A series of spin labeled acetycholine analogs, in which the number of methylene groups between the quaternary nitrogen and the alcohol oxygen ranged between 1-5, have been examined as inhibitors of electric eel acetylcholinesterase. Evidence is presented suggesting that inhibition of acetylocholinesterase by the spin labeled ACH analogs is due to the high affinity of these compounds for the enzyme, inhibition is competitive and reversible. It has been shown that complex formation is of major importance in the reaction between spin labeled ACH analogs and acetylcholinesterase. The acetylation step has been shown to occur by demonstrating that the leaving group is released as the reaction proceeds. Complex formation has been demonstrated by means of kinetic criteria. Kinetic parameter have been measured for the five compounds, and correlations with alkaline hydrolysis are disussed.
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D000818:Animals; D001665:Binding Sites; D002800:Cholinesterase Inhibitors; D004285:Dogs; D005399:Fishes; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D013113:Spin Labels; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D013113:Spin Labels; D000109:Acetylcholine