360 General Discussion 



cycle as a group of DPN-utilizing enzymes involving this substance 

 in a rapid reaction and that the respiratory chain regenerates DPN 

 in a slow reaction: 



fs-si!^ sloiv 



DPN > DPNH > DPN (Fig. IF) 



The dehydrogenase having the largest velocity constant for the 

 utilization of DPN would be able to operate at the lowest DPN con- 

 centration and would therefore win in competition with the other 

 members of the cycle. When one member of the cycle has won in the 

 competition and becomes the main source for DPN reduction, it is 

 then easy to apply the concept to the Michaelis affinity for a single 

 enzyme system. But in the competitive reaction, the important 

 quantity is the rate term k^ [DPN] [E]. 



Incidentally, I neglected to mention previously that when the 

 rates in the utilization and regeneration of the intermediate are 

 equal, there can be no control by that particular substance, as 

 indicated in Fig. IC3: 



equal equal 

 No control: ADP > A + P > ADP (Fig. IC3) 



Backer: I believe one could set up an experiment in glycolysis 

 which may resemble a positive feedback mechanism. For each 

 pyrophosphate bond of ATP expended there is a net return of 2 

 high-energy bonds formed during glycolysis. In the presence of 

 low ATP and high AMP the rate of glucose utilization should there- 

 fore increase until maximum efficiency is reached at saturating 

 ATP concentrations. 



Chance: Not really, because in electrical systems positive feedback 

 immediately leads to instability (unless it is counteracted by another 

 negative feedback). (See Fig. lA.) 



Backer: But there is net synthesis of 2 pyrophosphate linkages 

 for each glucose which is fermented. 



Chance: I still have difficulty in equating chemical synthesis to 

 electronic amplification. I suppose this is indicated by Fig. lA, 

 where the output of the amplifier is fed back to the input as a nega- 

 tive concentration. Chemicals do not simply disappear; they are 

 always converted to something else. 



Lehninger: To quote a good example: suppose you start with 

 pyruvic acid and the overall processes of its disappearance; you 

 need coenzyme A to make this. Let us say that some oxidation 

 product, past coenzyme A, is utilized as a building block for making 



