KINETICS OF ANALOG INHIBITION 251 



F.'(S') 



(S') + K, 



1+^ 



(2-4) 



If the disappearance of S or the formation of only P is measured, the inhi- 

 bition by S' will be typically competitive, but the inhibitor constant de- 

 termined by the plotting procedures, K^,, wiU not necessarily be a true dis- 

 sociation constant. The result wiU depend on the ratio kg.jkg, which in 

 most cases will be considerably less than unity. If P and P' are identical 

 and determined together, the inhibition wiU be less than in the previous 

 case. It is important in work with analogs to establish whether they are 

 catalytically reacted and, if so, to plan the inhibition experiments accord- 

 ingly. It is also necessary in many instances to determine initial rates, since 

 the concentration of the analog may be reduced significantly because of 

 its conversion to the product. 



The product, or one of the products, of the enzyme-catalyzed reaction 

 may generally be considered as an analog of the substrate, or of part of 

 the substrate molecule. Inhibition by products was taken up in Chapter 

 1-4 (page 140) and it was pointed out there that the inhibition is not 

 necessarily competitive, since the product can react with the enzyme or 

 other components of the reaction in a variety of ways. Several instances 

 of product inhibition will be encountered in this chapter and in none of 

 these is the inhibition due to a simple reversal of the forward reaction, 

 but to actual combination with the enzyme at or near the active center. 



A somewhat more complex situation, in which the analog is transformed 

 into a product that inhibits a subsequent reaction of the substrate, is fairly 

 common and warrants some discussion although a complete kinetic analysis 

 is difficult. The simplest system may be represented by: 



A --^ B A C (2-5) 



E. t 



A' — ^ B' (2-6) 



The substrate, A, and its analog, A', both are reacted by E^ and the analog 

 product, B', inhibits E,. There are several ways in which the rate can vary 

 with time and the behavior of the system will depend on many factors. 

 In the first place, the presence of A' may slow down reaction 1 whereby 

 A is transformed to B, this being a case of competing substrates. The for- 

 mation of C may thus be initially slowed for this reason. The concentra- 

 tion of B' will progressively rise and the inhibition on Ej increase. However, 

 the concentration of A' will decrease and the competition w^th A be reduced, 

 leading to a relative acceleration of reaction 1. The change in the rate of 

 formation of C will depend on the balance between these two types of 

 inhibition. For example, if A' is reacted fairly rapidly but B' is not a very 



