General Discussion 361 



coenzyme A, for making the catalyst. You are removing part of the 

 flux of the carbon through the scheme to go back and make catalyst 

 and to make your overall rate go faster. Can you call that a positive 

 feedback? Supposing the enzyme was rate-limiting. 



Chance: This question is similar to Prof. Potter's concerning 

 enzyme synthesis. It is certainly true that a synthesis of the rate- 

 limiting intermediate will cause an increase of the rate of overall 

 metabolism. In addition, an increase in the concentration of the 

 substances involved in such a synthesis will further increase the 

 rate. I will agree that this is positive feedback of the type that may 

 exist in the chemical system but, as I have stated above, the positive 

 feedback in the electrical system leads to instant instability. Altern- 

 atively, the effect could be regarded as an amplification. 



Backer: ATP formation in glycolysis occurs at later stages, far 

 removed from the initial steps of utilization. Why is that not a 

 positive feedback? 



Chance: Again I wonder whether it is really the analogue of the 

 electrical network in which it is possible to have positive and nega- 

 tive voltages ; in the direct chemical analogue you would need posi- 

 tive and negative ATP, but we do not have a negative ATP in the 

 chemical system. 



Backer: Can you consider ADP to represent "negative ATP"? 



Chance: I do not think this would be helpful. The chemical 

 analogue of the electrical feedback system avoids this difficulty and 

 satisfactorily represents the mass-law equations. 



Siekevitz: Negative and positive feedback may be all part of the 

 same picture if you consider the segregation of molecules. Product, 

 inhibition produces negative feedback if all the reactants are in one 

 compartment, but a positive feedback may occur when the product 

 is segregated across some barrier and cannot get back. Thus, the 

 reaction goes on to completion. The controlling factor may, thus, 

 have to do with membrane permeability. 



Chance : For a simple mass law system, the concentration controls 

 the rates. 



Siekevitz: It controls the rates if it is in the same compartment, 

 but what if the product always comes out into another compart- 

 ment? 



Chance: If segregation of the product by compartmentation 

 occurs, then this substance will become a rate-limiting intermediate, 

 since no regeneration occurs. This is, therefore, probably not a 

 feedback control of the type we are discussing here, unless there is a 

 leak from the compartment. I am sure I am being too rigid about 

 all this. 



Krebs: That is all to the good. 



