82 



3. KINETICS OF ENZYME INHIBITION 



the relative potency. It might be conchided that inhiliitors III and IV 

 are of comparable potency, although they actually differ by a factor 

 of 1000. 



INHIBITION BY REACTION WITH COENZYME 

 OR ACTIVATOR SITES 



It has been assumed in the inhibitions discussed up to this point that 

 the inhibitor interferes only with the binding or breakdown of substrate. 

 The inhibitor may also interfere with the binding or functioning of the other 

 possible components of the enzyme reaction. The general rate equation for 

 an enzyme reaction in which an activator and an inhibitor are both present 

 was developed by Friedenwald and Maengwyn-Davies (1954, p. 154) and 

 the following is an application of this equation to various special cases. 

 The reactions that must be considered in the general case may be represent- 

 ed as: 



EA 



/ 



% 



ES 



EA 



Ei 



- EAS 



- EIS ^=^ EAIS 



(3-56) 



EIA 



The rate equation can be written in terms of either substrate or activator: 



Vi = 



(3-57) 



+1 



(3-58) 



and they may be seen to be symmetrical with tespect to substrate and acti- 

 vator. The interaction constants expressing the effects of a component on the 

 binding of another may be defined as follows: a relates to I and S, /? to S 

 and A, y to I and A, and // to the effects of AS, IS, and lA on binding of I, 

 A, and S. That is, K^ = (E)(A)/(EA), y K, = (EI)(A)/(EIA), /? ^, - (ES) 

 (A)/(EAS), and jli K^ = (EIS)(A)/(EAIS), with similar expressions for K, 

 and K^. These general equations include effects of the inhibitor on both sub- 

 strate and activator; however, the formulation assumes that only the EAS 

 complex breaks down into products, i.e., the activator is essential and the 



