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ANNALS NEW YORK ACADEMY OF SCIENCES 



values of Eadie^ seem extraordinarily low, but these dissociation con- 

 stants have been calculated on the assumption that one molecule of 

 enzyme combines with two of inhibitor. Goldstein*' has discussed this 

 point and has claimed that Eadie's method of determining reaction 

 velocity involved a constant error. The titration of released acetic 

 acid, for twenty minutes, immediately following the addition of enzyme 



Table 2 



Dissociation Constants of Cholinesterase-Inhibitoh Complexes 



Dissociation constants calculated by method of Michaelis-Menten, except for 

 Straus & Goldstein values. Values for Ki at 37-38° . 



to a substrate-inhibitor mixture, corresponded to a stage of the reaction 

 where equilibrium had not yet been established, and where the reaction 

 velocities were higher than at equilibrium. This discrepancy was 

 greatest for concentrations of inhibitor producing moderate inhibitions. 



A second point of interest is the difference in the dissociation con- 

 stants of the complexes of the same inhibitor with cholinesterases of 

 different sources. Although the difference is not marked, it may be 

 seen that the constants for the morphine complex are 8.1 X 10~* for 

 human serum cholinesterase, and 14.6 X 10"* for dog serum cholin- 

 esterase. The occurrence, among different cholinesterases, of differing 

 sensitivities to inhibition by the same compound, will be discussed 

 further. 



In TABLE 3, are shown the concentrations of cholinesterase inhibitors 

 giving 50 per cent of the uninhibited cholinesterase activity. It will 

 be readily recognized that these values are equivalent to the values of 

 the dissociation constants, calculated by the Michaelis-Menten ex- 

 pression for non-competitive equilibrium. This table illustrates the 

 order of inhibition of different compounds. It may be seen that human 

 serum, rabbit serum, and human muscle cholinesterases are less sensi- 

 tive to inhibition by physostigmine than is the horse serum cholin- 



