General Discussion 359 



determines whether a particular reaction sequence is controlHng 

 and whether it is the concentration of the free enzyme or the con- 

 centration of the enzyme intermediate that is the control substance. 



Potter: Could this be extended directly to the situation of the 

 enzyme-forming sj^stem in which — in a sense — one does have an 

 amplifier, if the amount of enzyme is increased by net synthesis, not 

 just the amount of free enzyme? I think this is quite analogous. 



Chance: It is clear that under conditions where the enzyme con- 

 centration, E, is the control substance, an enzyme-forming system 

 would accelerate the metabolism. However, I do not feel that the 

 analogy to the electrical amplifier is an especially useful one. 



In Fig. IB, for instance, enzyme synthesis would increase the 

 concentration of reactant E, and hence would speed the rate of 

 formation of the intermediate over the metabolism. On the other 

 hand, if an enzyme were degraded, it would simply subtract from 

 the input to the control system and that would depress the amount 

 of enzyme. 



Potter: It would be worth while to discuss the situation in which 

 many enzyme systems, which have their own substrate, have a 

 reactant in common, e.g. ADP. When one of these systems uses up 

 a common substrate which affects the rate of reaction of other 

 systems, can this properly be referred to as feedback and, if not, 

 what should we call it? 



To get down to cases, our Chairman in his opening discussion 

 pointed out that if one member of the citric acid cycle is present in 

 large amount, it will repress the oxidation of the other members of , 

 the cycle. It may do this by means of a number of them using DPN, 

 for instance, so that the one which is present in large amount takes 

 over the DPN and makes it less available for the others. Can the 

 Michaelis constant be incorporated, and what should it be called? 

 It is really competition. 



Chance: It is appropriate to refer to the ADP control system 

 mechanism of Fig. IC in which ADP is utilized in a rapid reaction 

 and is regenerated in a slow reaction. It is possible that several 

 independent enzyme systems contribute ADP in parallel; the total 

 rate of production of ADP would be the sum of the individual rates. 

 Indeed, as in the case of glycolysis and respiration, there may be 

 more than one system expending thfe ADP supply. It is, therefore, 

 true that as one of the systems uses up the ADP, the other systems 

 will also be affected. To the extent that any metabolic regulation of 

 the type discussed here can be called a feedback, it is also appro- 

 priate to designate a multi-enzyme system in the same way (Potter, 

 V. R. (1957). Univ. Mich. med. Bull, 23, 401). Perhaps it is possible 

 to represent the DPN-linked dehydrogenases of the citric acid 



