350 



7. INHIBITION IN MULTIENZYME SYSTEMS 



as cyclic systems are frequently misleading when their characteristics are 

 obtained by general inspection. 



One of the characteristic features of cyclic systems is the constancy of 

 the total concentration of intermediates, which is not a restriction that 

 applies to linear sequences. As a consequence, a change in one intermediate 

 necessarily brings about changes in the others, with consequent changes in 

 the rates of those reactions. It is not, however, obligatory to assume such 

 constancy in (M)^ since one or more of the intermediates may be formed or 

 utilized in reactions outside the cycle, as is often the situation for the tri- 

 carboxylic acid cycle, in which case the kinetics presented here must be 

 extended. Before describing the effects of inhibition, it is of interest to 

 inquire into the changes brought about by alterations in (X) and (M)^. 



Effect of Substrate Concentration (X) 



The effects of varying (X) on the steady-state rate and concentrations 

 of cycle intermediates are shown in Fig. 7-16 for a system of arbitrarily 

 chosen constants and assumed (M),. As (X) increases, (C) falls and this re- 



- I 



-08 



-06 



-04 



0.01 



2 

 CAJ,(B) 

 orfO-nM 



lOOmM 



(X)- 



FiG. 7-16. Effect of the substrate concentration on the steady-state rate and con- 

 centrations of the intermediates in a cycUc system. Fj = 2, Fg = 1, F3 = 3, Xi = 1 

 mM, Kc, = 2 mM, A' = 1 ml/, A' = 0.5 mM, and (M), = 1 ml/. 



duces the rate of reaction 3 compared to a single enzyme system; i.e., the 

 rate does not rise as rapidly with (X) in the cyclic system as it would with 

 the isolated E3 where (C) would remain constant. Simultaneously, (A) and 



