General Discussion 857 



obvious features of gain stabilization (Fig. lA) or more favourable 

 dynamic response, etc., apply, and it is probable that a quite dif- 

 ferent set of theorems on feedback in chemical systems will be 

 evolved. Here and now, I wish to establish that the chemist and the 

 engineer refer to very different types of mechanisms. 



In a chemical reaction sequence, it is important to identify the 

 site of metabolic control in terms of the specific control chemical. 

 We can illustrate this by a system in which ADP is controlling. 



fast slow 

 ADP control: ADP > ATP > ADP (Fig. ICJ 



ADP is utilized in a rapid reaction, forming ATP through, e.g., the 

 respiratory chain. ATP is utilized in a slow reaction, which is rate- 

 controlling. The control substance, in so far as ADP utilization is 

 concerned, is ADP, and its site of action is the fast reaction. If the 

 slow step is saturated with respect to ATP, changes of the ATP 

 concentration have no efPect on the flow of metabolism. However, 

 any other system contributing to the rate of formation of ADP will 

 participate in the control of respiratory metabolism by alteration of 

 the ADP level. 



With a simple change of rate constants, the same system of 

 reactions can demonstrate ATP control. 



fdiSi^ slow 



ATP control: ATP > ADP > ATP (Fig. iCg) 



If ATP is expended in a fast reaction and ADP in a slow reaction,, 

 the regeneration of ATP is slow. Thus, the balance of formation and 

 utilization reactions determines which substance is rate-controlling. 



In these examples, metabolic control is exerted exclusively by the 

 slow step of both control mechanisms. In the cell the control 

 chemical may be produced and utilized by a variety of reactions. 

 The sum of the rate of these reactions is conveniently represented 

 (Fig. IB) by the steady state concentration of the control chemical 

 (ADP in Fig. IC^). For this reason it is much simpler to focus our 

 attention on the steady-state concentration of this control sub- 

 stance, since it represents the net result of a large number of pro- 

 cesses that cannot be measured individually. 



A single enzyme reaction affords an example of the regulatory 

 metabolic system. This is an especially useful example since many 

 properties of a single enzyme system are familiar to us. In this 

 case, the enzyme is utilized to form the enzyme-substrate inter- 

 mediate. If this is a fast reaction and if the intermediate is con- 

 verted back to the enzyme in a slow reaction, the flow of substrate 



