Geni^ral Discussion 363 



process, and it is in minimal concentration at one point in the cycle. 

 That cycle can be as long as you wish. It can extend from oxygen 

 to glucose to oxygen. 



Lipmann: On the other hand, in this long-chain reaction where 

 there are irreversible steps in between, the cycle is not really 

 reversible. The E is actually E plus some inhibitor. It is no longer 

 in equilibrium in any thermodynamic sense. Something has been 

 formed far back which now goes back and hooks on to the enzyme. 

 I wonder if there is any cyclic reaction. 



Potter: Up to this point we have been discussing straight-line 

 operations in which something goes along an unbranched pathway. 

 The essence of the problem is the fact that there are alternatives for 

 these metabolites. A given metabolite can go in two or more different 

 directions, and anything that is done to one reaction results in an 

 effect on the other reactions. We can stimulate one by inhibiting 

 the other one. This is our basic problem in metabolic control : how 

 do we effect this competition? When we consider the bacterial 

 synthesis of pyrimidines from carbamyl aspartic acid, which is 

 converted through many intermediates into uridylic acid and to 

 cytidylic acid, as has been shown by Dr. Pardee, and consider how 

 this is controlled in the bacterial cell we may say that uracil can 

 produce uridylic acid, which can form cytidylic acid, and the latter 

 by negative feedback can shut off the synthesis of itself from aspartic 

 acid. The important point is that in either case the cell gets cytidylic 

 acid and grows, so that this particular feedback mechanism is simply 

 a device for growing under economical conditions, choosing whether 

 growth shall be from uracil or from carbamyl aspartic acid. 



Another important point is that when a liver cell is confronted 

 with both aspartic acid and uracil it still does not make more liver 

 cells; it somehow decides not to make thymidylic acid even though 

 it has both uracil and aspartic acid. One of the ways in which it 

 can do this is by disposing of some intermediate in such a way that 

 thymidylic acid synthesis does not take place. 



My first point was that the essence of metabolic control is the 

 choosing between alternatives. Finally, in animal tissues we have 

 to prevent certain things such as DNA from being synthesized in 

 certain tissues, even when all the normal distal building blocks are 

 present. 



Krehs: The choosing of alternatives could be interpreted as feed- 

 back. 



Chance: If a metabolic system is to be able to select between 

 alternatives and at the same time to be maintained "under control" 

 in the sense in which we have been discussing it here, there must be 

 suitable control mechanisms for the two pathways which we will 



