102 



3. KINETICS OF ENZYME INHIBITION 



Table 3-1 

 Effect of Inhibitors on the Forward and Reverse Reactions" 



h 



Km 



s 



Km 



I 



if 



Mechanism 3-104 



Uninhibited Inhibited 



10-3 

 10-8 



10-^ 



io-« 



10-3 



10-3 



10-3 



1 



10-4 



10-8 



10-10 



io-« 



10-^ 

 10-* 

 10-* 

 10-2 

 0.82 

 0.10 



Mechanism 3-105 



Uninhibited Inhibited 



10-* 

 10-' 

 10-5 



io-« 



10-' 

 10-3 

 10-3 

 10-* 

 10-3 

 10-* 



10-* 

 10-' 

 10-s 



io-« 



10-8 



10-* 



10-3 



10-* 

 1.83x10-* 

 1.81x10-* 



0.83 



0.07 



Inhibited 



10-* 

 10-' 



io-« 



10-6 



io-« 



10-* 



10-3 



10-2 

 1.75x10-3 

 1.89x10-3 



0.33 

 -2.11 



" Kg and A'j, are true dissociation constants whereas K^ and Km are Michaelis 



s p 



constants. In all cases (S) = (P) = 10-3 31. The negative vakie of v in the last column 

 indicates stimulation. 



quence; different dyes may accept from different components, as illustrat- 

 ed in the following diagram where the hydrogen-atom or electron path is 

 indicated by arrows: 



oMn 



X, -> X, 



\ 



D 



X. 



\ 



(3-107) 



D' 



The various components of the enzyme complex (X^, X2, etc.) may be 

 bound metal ions, flavine dinucleotides, nicotinamide dinucleotides, or 

 any substance that is oxidized and reduced in the transport. An inhibitor 

 may depress the rate markedly when one dye is used and scarcely at all 

 with another dye; such would be the case if the inhibitor interfered with 

 either component X2 or X3 above, reduction of D' being inhibited without 

 action on D reduction. Heavy metal chelating agents, such as 1,10-phe- 

 nanthroline, inhibit potently the reduction of triphenyltetrazolium dyes 

 by several dehydrogenase systems but have little effect on reduction of 

 dichlorophenol-indophenol. Since a great deal of work has been published 

 on " dehydrogenase " inhibition using the dye reduction technique, it is 



