60 3. KINETICS OF ENZYME INHIBITION 



This leads to the following equations for the rate and inhibition: 



Ki' 



(I) +K,'\ (S)+A%{A','/[(I) +K,']} 



(I) 



(I) + K,' [1 + A,/(S)] 



(S) 



(3-24) 



(3-25) 



The rate expression shows that the inhibitor reduces both F„, and K^. Such 

 inhibition is recognized by the family of parallel lines obtained by plotting 

 l/Vj against 1/(S) or l/v, against (I) (see Chapter 5), but as Dixon and Webb 

 (1958, p. 179) have pointed out, this method does not distinguish between 

 this type of inhibition and the situation in which K^,^ — Jc^jJcj and the inhi- 

 bitor in some manner decreases ^2- 



Examples of coupling inhibition are uncommon. The inhibition of cyto- 

 chrome oxidase by azide (Winzler, 1943) and of pepsin by hydrazine (Scha- 

 les et al., 1948) may possibly be of this type. The inhibitions of the aryl- 

 sulfatase of Alcaligenes by cyanide and hydrazine (Dodgson et al., 1956) 

 would appear to be the best documented examples of coupling inhibition. 

 Not only were the 1/^^—1(8) and ili\ — (I) plots clearly a family of parallel 

 lines, but the pH-dependence of the inhibitions showed a dissociating group 

 present in the ES complex but absent in the free enzyme. It is likely that 

 a similar mechanism must be assumed in the complexes formed between 

 a variety of inhibitors (bisulfite, sulfide, cyanide, hydroxylamine, and various 

 mercaptans) and the E-DPN* complexes of various dehydrogenases (Eys 

 et al, 1958). 



Classification of Inhibitions by Reiner 



Reiner (1959, p. 148) has suggested a new terminology for the classifica- 

 tion of enzyme inhibitions in order " to avoid the unnecessary connotations 

 of the usual terminology." The correspondence between the two systems 

 can be easily made: 



inclusive inhibition = noncompetitive inhibition 



exclusive E inhibition = competitive inhibition 



exclusive C inhibition ~ coupling (uncompetitive) inhibition 



These inhibitions were further subdivided into complete and partial and the 

 use of these terms corresponds exactly to the similar terms in the treatment 

 above. Reiner points out that the designation " competitive " suggests that 

 the substrate and the inhibitor complex with the same active site on the 

 enzyme and compete for this site, whereas there are numerous other mecha- 

 nisms whereby substrate and inhibitor could interfere with each other's 

 binding to the enzyme. Unfortunately, there are probably no terminologies 

 that will fail to evoke some unnecessary connotations or erroneous interpre- 



