Stojan_1991_Biochim.Biophys.Acta_1079_96

Some investigation in this laboratory pointed to an unexpectedly slow inhibition of cholinesterase by D-tubocurarine, occurring in addition to a typically instantaneous inhibition. In order to elucidate this phenomenon, the hydrolysis of butyrylthiocholine catalyzed by cholinesterase was recorded, in the absence and presence of D-tubocurarine, on a stopped-flow apparatus. Experimental results were analyzed by classical kinetic methods and by means of mathematical modeling. It was found that the inhibition is of a double character, consisting of an instantaneous phase and a slow one occurring in a minute time scale. It seems that the action of D-tubocurarine is a consequence of an instantaneous binding of D-tubocurarine to a peripheral site, followed by a relatively slow conformational transition in the enzyme.