SUBSTRATE INHIBITION 119 



It is likely that the majority of inhibitions will be noncompetitive inas- 

 much as secondary groups in the active center that would bind the sub- 

 strate in inactive complexes must be uncommon. Noncompetitive and coup- 

 ling inhibition lead to equations indistinguishable experimentally from those 

 of type A inhibition (Eqs. 4-2 and 4-7), so that the interpretation of the de- 

 termined constants is arbitrary unless additional evidence indicates the 

 mechanism. It may be noted that the usual formulation of type A inhi- 

 bition by Haldane is essentially identical to coupling inhibition of type B 

 as far as kinetics are concerned. The rate-pS curves for the major types of 

 inhibition are shown in Fig. 4-4 and the effect of variation in affinity for 



ps 



Fig. 4-4. Variation of the rate with the substrate concentration for type B sub- 

 strate inhibition of different kinds (scheme 4-8). V .^ = 100, K^^\ m.M, and y = 2. 

 Curve 1: competitive inhibition; curve 2: noncompetitive inhibition; curve 3: 



coupling inhibition. 



the inhibiting substrate molecule is illustrated in Fig. 4-5 for noncompeti- 

 tive inhibition. The shift in peak upwards and to higher substrate con- 

 centrations with decreasing affinity is evident. Inhibition has been con- 

 sidered only with respect to interference with substrate, but a second mol- 

 ecule of substrate can also, of course, interfere with the binding or reacti- 

 vity of a coenzyme, activator, or acceptor. The appropriate rate equation 

 can be obtained by simple substitutions in the equations given in the pre- 

 vious chapter. 



If the rate at high substrate concentrations does not continue to fall 



