SUBSTRATE INHIBITION 



139 



mate, it illustrates a method which could be quite accurate. These curves 

 also show that over a certain range of substrate concentration, the rate 

 of the control is decreased and the rate of the inhibited enzyme is increased 

 by a rise in the substrate concentration, the inhibition by 284C51 falling 

 from 100% to less than 50%. It is possible that in vivo at localized end- 

 plate or synaptic regions the acetylcholine reaches concentrations in this 

 range and that the kinetics of inhibition follow the formulations presented 

 in this section. 



150 



CONTROL 



100 



50 



INHIBITED 



2 5 



05 



ps 



Fig. 4-15. Effect of the inhibitor 284051 on the rate-pS curve of substrate inhibition 

 of human erythrocyte acetylchoHnesterase. (I) = 1.3 X 10~^ mill. (From Austin 



and Berry, 1953.) 



Inhibition of various tissue cholinesterases by physostigmine (3.63 X 10~^ 

 mM) produced an average shift of pSo from 2.57 to 1.40 and a depression 

 in Vq of 85%, conforming to predictions. Another inhibitor, clupeine, of a 

 less specific type, also reduced the pSo to an average value of 1.92 but 

 produced only a 5% depression of Vq (Augustinsson, 1948). Gum arable, 

 which stimulates cholinesterase slightly, shifted the pSo upwards to 2.75. 

 It should be noted that a marked shift in pSo means that a substance 

 inhibits a reaction in one range of substrate concentration and stimulates 

 it in another range. The nature of the response to an inhibitor in such 

 systems is strongly dependent on the substrate concentration. 



