858 General Discussion 



through the system is regulated by the enzyme concentration, 

 provided an excess of substrate is present. 



E + S > ES 



ES > E + P 



(Fig. ID) 

 fast slow 

 Enzyme control : E > ES > E 



fast slow 

 Intermediate control : ES > E > ES 



This is a basic example of a metabolic system regulated by enzyme 

 concentrations and it may therefore cover some of the cases referred 

 to by Dr. Magasanik. It is obvious that synthesis of the enzyme will 

 increase the metabolic flux. 



The last line of Fig. ID represents an enzyme system operating at 

 low substrate concentrations. Here the enzyme-substrate compound 

 is the rate-limiting component and its breakdown is the rate- 

 limiting reaction. 



It may be mentioned in passing that substrate control of an 

 enzyme system does not directly involve a feedback, since the 

 product of the enzyme activity is not identical with the substrate. 

 However, if subsequent reactions produce substrate, the type of 

 control considered here may be obtained. 



The differential equation for a single-enzyme system also sheds 

 light upon the general properties of metabolic control : 



•^ = ki (e-p)x - kgp 



formation utilization 



(Fig. IE) 



^ = kix(e-p) 

 utilization 



The steady state concentration of the rate-limiting intermediate is 

 dependent upon reaction rate terms involving the products of 

 various concentrations. For a single-enzyme system, only the pro- 

 duct of the enzyme and the substrate concentrations are involved 

 and the rate of utilization of the intermediate is proportional to its 

 concentration; for more complex systems, other terms are involved. 

 The overall balance between rate of formation and rate of utilization 



