614 



13. REVERSAL OF INHIBITION 



here because he assumed that the activity was zero at the start of the 

 displacement. 



The difference between the assumptions of Goldstein and those made in 

 the present treatment is easily explained. If the rate of combination of the 

 substrate with the enzyme is slow so that the rise in activity is related to 

 this as well as to the dissociation of the EI complex, then the activity 

 must be set equal to zero at the start, as Goldstein did. Here we assume 

 that the reaction of the substrate with the enzyme is rapid and is com- 

 plete before appreciable loss of the inhibitor from the enzyme has occurred. 



200 



TIME (VIIN 



Fig. 13-4. Displacement of physostiginine from serum cholinesterase 

 by acetylcholine. (From Goldstein, 1944.) Curve A: (I) = 5.5 X 10-^ 

 milf; curve B: (I) = 1.35 X 10-^ mi/; curve C: (I) = 5.5 X 10-^ ml/; 

 curve D: (I) = 5.5 X 10-^ mil/; curve E: (I) == 5.5 X 10-' mil/. 



The experimental curves for the reversal of the physostigmine inhibi- 

 tion of cholinesterase following the addition of acetylcholine are shown in 

 Fig. 13-4 for different concentrations of physostigmine (Goldstein, 1944). 

 The curves are quite adequately fitted by Eq. 13-16 but not by the equation 

 derived by Goldstein because, in this case, the combination of the acetyl- 

 choline with the free enzyme is much more rai^id than the dissociation of 

 the physostigmine from the enzyme. The first readings after addition of 



