546 12. RATES OF INHIBITION 



inh bitor. For the two lower concentrations, A^^ may be estimated as approx- 

 imately 0.094 liters mole"^ sec~^ but at the higher concentration of 25 mM, 

 the rate is less than half what would be expected. Such a deviation at high 

 inhibitor concentrations is often observed and sometimes it may be due 

 to the fact that the EI complex is not formed directly upon collision of the 

 inhibitor molecule with the active enzyme site but requires a further reac- 

 tion of some type, which may limit the rate at high concentrations of the 

 inhibitor. 



0.8- 



0.6 - 



0.4 - 



0.2 - 



Fig. 12-8. Inhibition of plasma cholinesterase by HgCla (0.227 mM) with time. 

 (From Goldstein and Doherty, 1951.) 



The inhibition of lactate dehydrogenase by y^-chloromercuribenzoate 

 (p-CMB) presents an interesting situation because the reaction of the in- 

 hibitor with the enzyme can be followed spectrophotometrically by meas- 

 uring the changes in the optical density at 250 m// as the sulfhydryl groups 

 are combined (Neilands, 1954). The time courses of the sulfhydryl reaction 

 and the inhibition are compared in Fig. 12-11 and, altiiough the concen- 

 trations of p-CMB were different in the two experiments, comparable rates 

 are evident. The rate of the reaction of p-CMB with lactate dehydrogenase 

 is much slower than with most other susceptible enzymes indicating that 

 the sulfhydryl groups necessary for activity are partially protected in some 



