The enzymic hydrolysis of alkyl fluoroacetates and related compounds

Publisher Website
Google Scholar
Abstract
Esters of halogenoacetic acids possess a bell-shaped pS-activity curve when hydrolyzed by specific or unspecific esterases. For the homologous series of n-alkyl fluoroacetates, hdyrolyzed by acetylcholine esterase, the pS (log of substrate concn.) opt. shifts to higher values with increasing chain length, and the max. rate of hydrolysis increases. Fluoroacetates with a branched alkyl chain have a much lower rate, the effect being greater with choline esterase than liver esterase. This fact supports the assumption of nucleophilic attack of a group in the esteratic site on the carbonyl carbon of the ester. Esters with a very low rate of hydrolysis may prove to be efficient, revers- ible inhibitors of acetylcholine esterase, although, no such case was observed on liver esterase. The pKm (Michaelis-Menten constants) values of the system ethyl halogenoacetates-liver esterase can be represented as a linear function of pKa (acid dissociation constants), thus obeying the Hammett equation pKm = A.pKa + B. The corresponding curve for choline esterase, however, possesses a max. for chloroacetate, whereas fluoroacetate behaves abnormally.