84 3. KINETICS OF ENZYME INHIBITION 



which is quite comparable to Eq. 3-28 applying to competition with sub- 

 strate. Again, if /?7^ 1, the inhibition is modified by this factor. The ef- 

 fects of the factor /5 on determinations of the various dissociation constants 

 will be discussed in Chapter 5. 



Inhibition with Respect to a Coenzyme 



Since the equations for reaction rate are identical for activators, coen- 

 zymes, or second substrates (see Eqs. 2-61 and 2-72), when there is no effect 

 of these on substrate binding, it is evident that similar equations are ob- 

 tained for noncompetitive and competitive inhibition with respect to these 

 components. In fact, under these conditions, competition with any com- 

 ponent X will lead to an equation of the form: 



' - (I, +"(xo + 1 '^-««' 



and with similar corrections when the substrate binding is modified by 

 the presence of the component. Similarly, noncompetitive inhibition will 

 always result in an equation i = (r)/[(r) + l] which is independent of com- 

 ponent concentration. It must be emphasized that this is not the case if 

 substrate binding is altered by the presence of the other component. 



An example of this type of mechanism for which the kinetics have been 

 studied experimentally is the inhibition of yeast alcohol dehydrogenase by 

 o-phenanthroline (Hoch et at., 1958). The enzyme active center contains 

 an atom of zinc that is necessary for the binding of DPN+ and DPNH; 

 the metal chelator, o-phenanthroline, inhibits the reaction by complexing 

 with the zinc and competing with the coenzyme. The inhibitor, on the other 

 hand, does not compete with either ethanol or acetaldehyde, and thus the 

 zinc must be involved only in the binding of the coenzyme. 



Competitive Inhibition with Respect to an Activator Essential for Binding 



of Substrate 



When the primary function of the activator is the binding of the substrate 

 to the enzyme, as it may often be in the case of metals, and the inhibitor 

 blocks the activator from the enzyme, an interesting type of inhibition re- 

 sults. This situation may be represented as: 



K > EA ^ r- 

 E EA8->E + P (3-67) 



N 



^' EI 



