628 



13. REVERSAL OF INHIBITION 



(OR), 

 EH + P=0 

 X 



(OR), 



^ EH---P=0 



I I 



X 



(2) 



(OR), 



E-P=0 



+ 

 HX 



(OR), 

 HjO I 

 > P = + EH (13-37) 



(3) 



OH 



This is very similar to the hydrolysis of acetylcholine by the enzyme and 

 presumably the same active site groups are involved. The inhibition by the 

 dimethyl compound is due to the fact that reaction 3 is very slow and this 

 allows the accumulation of the EI complex. For the diethyl compound, it 

 is apparent that reaction 3 is too slow to measure. The reversal reaction 

 is an hydrolysis of the phosphorylated enzyme. Its rate is independent of 



2.0 



,100 



TIME (MIN) 



Fig. 13-10. Spontaneous reversal of inhibition of rabbit erythro- 

 cyte choHnesterase inhibited by dimethyl-79-nitrophcnyl phos- 

 phate plotted on a logarithmic scale to show the first-order 

 kinetics. (From Aldridge, 1953 b.) 



the group X but is related to the group R, since R can modify the electronic 

 configuration and charge around the phosphorus atom and hence alter its 

 reactivity with water. 



The maximal inhibition produced in such cases may be expressed easily. 

 The over-all reaction of the inhibitor is: 



e + I;4ei4e + q 



(13-38) 



where Q is the product formed by the action of the enzyme on the inhibitor. 

 Thus: 



A-:(E,)(I) 



(EI) = 



k,{I) + A:_i + h 



(13-39) 



