362 General Discussion 



Lipmann: I am at a loss if this is put into equations. But I feel 

 that most of what we call feedback mechanisms maybe rather simply, 

 and without further formalization, described as the regulation of 

 supply and demand. The regulation of the rate of respiration by 

 the acceptor effect, the availability of ADP, is a good example of 

 that. 



Krehs: The term feedback, as used by engineers, has been defined 

 as control of input by output. 



Potter: I should like to hear Dr. Pardee and Dr. Magasanik com- 

 ment on some of these points. They both have excellent examples of 

 chemical feedback. 



Pardee: I am at present more interested in experimental results 

 and prefer not to attempt a definition. 



Magasanik: There seems to be one difference between the energy- 

 yielding systems which we have discussed during the last two days, 

 and the systems involved in biosynthesis of amino acids, purines, 

 etc. which we have discussed today; and that is that the control in 

 the former case is through equilibrium reactions, reactions that can 

 essentially go forward and backwards, and that it is the level of the 

 substrates which controls the rates of the reactions ; whereas in the 

 biosynthetic sequences many steps are irreversible: the reactions of 

 biosynthesis are being driven towards the formation of protein. 

 There, of course, since a regulation by equilibrium is not possible, 

 the regulation is effected by having the products act as specific 

 inhibitors of earlier steps. This seems to be a fundamental difference 

 which may have physiological significance for the cell. 



Krehs: I do not agree that there is a fundamental difference. 

 All these control mechanisms have an aim, namely to maintain a 

 steady state system. In the energy-yielding reactions, the aim is to 

 keep a supply of ATP. In the biosynthetic reactions, it is to supply 

 a basic pool of e.g. amino acids. The supply comes to a stop when 

 the pool of amino acids is sufficient to maintain the synthesis of 

 protein. 



Lipmann: I think that a higher mode of construction has to go 

 into the control mechanism. When the end product of a reaction 

 series inhibits an enzyme which is quite far back along the line, this 

 has nothing to do with equilibrium; it is just construction. 



Krehs: What you say appeals to me. If we assume that every 

 catalyst constitutes a feedback system (as Prof. Chance has sug- 

 gested), then we rather dilute the concept of feedback. 



Chance: The point is that the top equations are probably similar 

 to the bottom ones. The relationship is that the controlling inter- 

 mediate is behaving mathematically like an enzyme, i.e. it is 

 utilized and is regenerated in a cyclic fashion, it is not lost in the 



