446 



9. INHIBITION IN CELLS AND TISSUES 



(b) Case 2: one enzyme and two substrates 



If a noncompetitive inhibitor affects the rate for each substrate equally, 

 which is likely but not necessary, the inhibition on the total reaction will 

 be the same as for the individual reactions, but for competitive inhibition 

 the problem is more complex because competition with the two substrates 

 may be different. Also the same effect noted in case 1, the effect of total 

 substrate concentration, will occur here. The situation actually involves 

 competition for an enzyme by two substrates and an inhibitor. In this case 

 not even the l/v, against (I) plot will be linear since: 



Vi = 



+ 



(9-4) 

 (c) Case 3: two enzymes and one substrate 



When only one of these enzymes is inhibited noncompetitively to the ex- 

 tent i, the inhibition on the total system will be ^, = i (vjvi) in case the 

 endogenously active enzyme is affected and i[ = i [vjv,) when it is the en- 

 zyme acting on the added substrate that is affected. The inhibition on the 

 enzyme is thus quite easy to calculate if the endogenous controls are run. 

 The plots of Ijvi against either 1/(S) or (I) will be nonlinear, but plots with 

 1/v (where v is obtained by correction for the endogenous metabolism) will 

 be linear. Similar conclusions apply to competitive inhibition. It may be 

 noted that when the inhibitor acts on both enzymes, i\ on the enzyme re- 

 sponsible for the endogenous activity and ^ on the enzyme acting on the 

 added substrate, the total inhibition is given by: 





(9-5) 



where v. is the endogenous rate and v is the rate due to the added substrate. 



(d) Case 4: two enzymes and two substrates 



Since the rates of the separate reactions are additive, what has been 

 said about case 3 applies equally here. There is perhaps more opportunity 

 for a specific inhibition of one enzyme than in the previous case. 



It is important to examine the effects of the substrate concentration on 

 inhibition in systems with two or more enzymes. The total inhibition of 

 the system when the enzyme depressed is the one acting on the added sub- 

 strate may be written as: 



(I) 

 (I) + K, 



(9-6) 



