KINETICS FOR THE INHIBITION OF CARBOXYLESTERASE BY MALAOXON

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Abstract
Malaoxon and carboxylesterase undergo two separate but simultaneous reactions when mixed in solution. One results in the irreversible inhibition of carboxylesterase. In the other, malaoxon acts as a substrate and is hydrolyzed.This work is concerned primarily with the inhibition reaction, although direct evidence of the substrate reaction is also given. It seemed possible that inhibition could occur by two mutually exclusive routes. Equations were derived for each of the two routes, and both equations gave identical and unambiguous expressions for ki, the bimolecular velocity constant of the inhibition reaction. A procedure for determining the kivalues of malaoxon and of four carboalkoxy homologues of malaoxon in reaction with partially purified rat-liver carboxylesterase is described. Evidence is given which suggested that the substrate reaction was controlled by the acylation step. This in turn suggested that useful estimates of the binding (Ka) and phosphorylation rate constants (k2p) could be made. Values for kiand tentative values for k2pand Kaare given.