FACTORS IMPORTANT IN INHIBITION 101 



where K, and Kp refer to either dissociation or Michaelis constants depend- 

 ing on the conditions. The inhibition of forward and reverse reactions in 

 the noncompetitive case would be: 



. _ _(I) . ^ (I) 



and if = i^ since the K^s must be equal, the binding of the inhibitor being 

 unaffected by the presence of either substrate or product. Thus noncom- 

 petitive inhibition is the same in both directions. Competitive inhibition is 

 expressed by: 



. _ (I) . _ (I) (3 IQg. 



'' ~ (I) -I- K,^ [1 -1- {S)IK,] '' (I) + K,^ [1 + (P)/^.] 



and it is evident that if will generally not equal i., because competition of 

 the inhibitor with substrate will usually be different from that with pro- 

 duct. This applies to mechanism 3-105 where there may be different sites 

 for binding of substrate and product; if they are bound at the same site, 

 as in 3-104, K, = K, but K, and K,, may be different. In partially com- 

 petitive inhibition or mixed inhibition K^ may differ from K^ also. 



One may demonstrate various differential degrees of inhibition by taking 

 the general values of the constants for mechanism 3-105 (see Eq. 2-18) 

 and assigning various values to the rate constants for the uninhibited and 

 inhibited reactions, bearing in mind that Eq. 2-19 imposes certain restric- 

 tions if the over-all equilibrium is to remain unaffected. Some examples 

 are given in Table 3-1 to illustrate possible types of inhibition. It is possible 

 that the reaction in one direction is inhibited while that in the other direc- 

 tion is accelerated. There is little basis for prediction of the behavior in any 

 system unless all the constants and the changes in them induced by the 

 inhibitor are known. 



If the inhibitor combines with either the substrate or the product, this 

 naturally leads to a specific inhibition of one direction of the reaction. This 

 may be a factor even though it is not the primary mechanism of the inhi- 

 bition. 



Inhibition of Acceptor Reduction 



It is a common procedure to measure the rate of an oxidation reaction 

 by a determination of the reduction rate of some coenzyme or dye. Much 

 work on dehydrogenases has been done using methylene blue as a hydrogen- 

 acceptor and within the past few years a number of versatile acceptors have 

 been introduced into enzymology. Certain problems may arise in connec- 

 tion with inhibitor study. The dye usually does not accept directly from 

 the substrate but from one of the enzyme components in the transport se- 



