General Discussion 367 



sequence, e.g. in glycolytic or respiratory enzymes which — in some 

 organisms at least — are probably not adaptive, whether such a 

 built-in feedback was selected or whether it was just pointed to by 

 man with pride so that he could say "Here I can see the secret of 

 life". 



Potter: It was not selected. It was simply that if it had survival 

 value it survived. That is all there is to it. 



Lehninger: There is another and much simpler instance, i.e. the 

 hexokinases: some are inhibited by glucose-6-phosphate and some 

 are not. There must have been some element of survival value in 

 one or the other kind of hexokinase. 



Potter: In a particular constellation of enzymes. 



Mcllwain: A general point is that enzyme specificity as a whole 

 will be subject to evolutionary control or selection: the question of 

 what range of substrate will be affected by a given enzyme. 



de Duve: If I understand Prof. Chance rightly he defined a con- 

 trolling substance as a catalyst which can exist in two different 

 states, and which functions in a cycle linking two processes together. 



Chance: I do not think that the controlling substance is neces- 

 sarily restricted to a catalyst ; it can also be a coenzyme, provided it 

 is in a form that can shuttle about. 



de Duve: That is the point I was driving at. The controlling 

 substances of most general importance, according to that definition, 

 must be the coenzymes, because they happen to link the greatest 

 amount of different reactions together. Another aspect of this is 

 that the total amount of coenzyme acquires an important regulating 

 function when it falls below optimum. If the amount of coenzyme 

 decreases as the result, for instance, of an avitaminosis, then the 

 competition between apoenzymes for this limited coenzyme becomes 

 more and more important. The fact that reactions become deficient 

 one after the other as the avitaminosis proceeds might be explained 

 on this basis and one might surmise that the first enzyme to become 

 defective will be the one with the lowest affinity for the coenzyme. 



Chance: I would like to refer again to the discussion of Fig. IF 

 (p. 360) in which we considered the possible coenzyme limitation of 

 the citric acid cycle activity. Under such conditions, the enzyme 

 system with the highest affinity for the coenzyme was already con- 

 trolling the metabolism. In such a situation, a lowering of the 

 coenzyme concentration would further enhance the control exerted 

 by this reaction. If one considers the simultaneous function of 

 pyridine nucleotide in the citric acid cycle and in glycolysis, then 

 one system becomes deficient after the other, as you have pictured 

 it. 



Backer: Prof. Lynen has given us a stimulating discussion on the 



