ENZYMES 145 



rcvcise reaction begins. 1 lie overall reaction rate at any instant is 

 the difference between the absolute rates of the two individual re- 

 actions, and the reverse step is shown to depend upon [H3O+]. Start- 

 ing with pyruvate, the pH plays an initial and continuing role and 

 becomes a key factor in the rates of enzyme systems like these. Thus 

 a shift in pH changes not only the extent of reaction as predicted 

 from the equilibrium constant but the net rate of reaction as well. 



Inhibitors 



Any substance whose presence reduces the rate of an enzyme reaction 

 is called an inhibitor. The use of the word substance excludes the 

 ordinary physical factors like heat; however, it does include a number 

 of protein denaturants that reduce reaction rates by irreversibly 

 destroying the enzymes. These general reagents include strong acids 

 or alkalis, strong oxidizing agents, trichloroacetic acid, and several 

 heavy-metal ions. Their mode of action is quite clearly a simple matter 

 of reduction in the concentration of active enzyme. 



Another type of inhibitor is much more specific, affecting only 

 certain systems. These compounds are believed to form reversible 

 complexes with the specific enzymes but complexes which do not 

 react to form products. Assuming that enzyme E and substrate S form 

 a complex ES which decomposes into enzyme plus products P, the 

 following equilibrium may be written: 



E + S±^ES±^E + P 

 In the presence of one of these inhibitors I, 



E + I ±^ EI 



without a subsequent step leading to any products other than enzyme 

 and inhibitor. Thus the inhibitor competes with the substrate for 

 the enzyme and decreases the net amount of enzyme available for 

 reaction with the substrate. According to 



^3[E][S] 



V = 



Km + [S] 



from page 138, the reaction rate automatically must be decreased. 

 It is also apparent from this equation that when [S] is smaller than 

 K^ an increase in [S] increases the rate. Hence the addition of sub- 

 strate tends to overcome the effect of the inhibitor. This competition 

 between substrate and inhibitor occurs when enzyme and inhibitor 

 interact reversibly to form a complex to which the substrate does not 

 attach. Inhibitors of this group are termed competitive. 



