126 



4. SUBSTRATE INHIBITION AND PRODUCT INHIBITION 



esteratic site to bind and liydrolyze the ester group. In conformity with the 

 suggestion of Haldane, they explained substrate inhibition in terms of 

 the binding of two molecules of acetylcholine in an inactive complex. 



E 



^ 



KJ 



KJ 



W 



Such inhibition occurs only with acetylcholinesterase (true cholinesterase) 

 from erythrocytes and mammalian tissues, and not with the pseudo- 

 cholinesterases of serum (Alles and Hawes, 1940). Inasmuch as the rate-pS 

 curves for human erythrocyte acetylcholinesterase are somewhat asymmet- 

 rical, Myers (1952 c) concluded that the ESg complex was partially ac- 

 tive. Using an equation of the type 4-12 he showed that a value of ^ ^ 0.1 

 accounted satisfactorily for the experimental data, i.e., the activity of the 

 ESg complex is one-tenth that of the ES complex. 



Fig. 4-11. Substrate inhibition of acetylcholinesterase at different salt concentra- 

 tions. (From Alles and Hawes, 1940.) Curve 1: 0.0059 31 NaCl; curve II: 0.145 M NaCl. 



Increase of the ionic strength alters the form of the rate-pS curves in a 

 characteristic way (Alles and Hawes, 1940). A change of NaCl concentration 

 from 0.0059 M to 0.145 M shifted the pSo from 2.25 to 1.80 and led to an 

 asymmetry as shown in Fig. 4-11. Increasing the ionic strength slows the rate 

 at low substrate concentrations and accelerates it at high substrate concen- 



