310 Discussion 



of such importance for the survival of an organism that, in the course of 

 evolution, selection will occur for the ability to form two enzymes 

 catalysing the same reaction, but differing in their sensitivity to a 

 controlling metabolite. 



Racket : I am not sure that this answers Prof. Lipmann's question. 



Lipmann: My question is difficult to answer, as has just been proved! 

 It is not meant to be answered. I would only emphasize that the synthe- 

 sis of an enzyme is complicated if you not only have to make a protein 

 which has a site for a substrate, but also a site for the inhibitor. 



Pardee : I wonder whether there are two sites. Perhaps the difficulty 

 is more in the eye of the organic chemist than in the structure of the 

 compound. In the case I mentioned, there is a competitive inhibition, 

 and the simplest way of looking at it is that the substrate and the 

 inhibitor compete with each other for a site. 



Lipmann: But cytidylic acid and carbamyl phosphate are very dif- 

 ferent. 



Pardee : They look very different, but perhaps we cannot see how they 

 are shaped to be competitors. 



Lipmann : There are many steps in between. Still, it has to be built 

 for it in some way. 



Pardee : Selection in bacteria is very fast. In the evolutionary process 

 it takes only a matter of days for one mutant with a selective advantage 

 to grow a population and reach the steady state in which it has over- 

 whelmed the original type. 



Potter: I disagree with an earlier comment made by Dr. Pardee. I 

 think he was conservative when he extrapolated to animal tissue. He 

 expressed the opinion that in animal cells, perhaps in contrast to 

 bacterial cells, after the cells were formed the amounts of enzymes re- 

 mained constant. I have been collecting literature on this subject. 

 There are some very clearcut cases in which the amount of enzyme has 

 changed dramatically in animal tissues over short periods of time 

 under conditions which must involve feedback control, where new cells 

 have not been formed. 



Krehs: Have you in mind e.g. the cases reviewed by Knox and co- 

 workers where enzymes are formed adaptively in animal tissues in 

 response to dietary changes (Knox, W. E., Auerbach, V. H., and Lynn, 

 E. C. C. (195G). Physiol. Rev., 36, 164)? 



Potter : That is one example. An interesting case is that of Rosen and 

 co-workers, on the glutamic-pyruvic transaminase induced by the 

 administration of cortisone, dehydrocortisone or prednisone (Rosen, F., 

 Roberts, N. Q., Budnick. L. E., and Nichol, C. A. (1958). Science, 127, 

 287). 



Krehs: The urea-forming system in the liver becomes much more 

 active if one keeps rats on a protein-rich diet for a few days. In my 

 introductory talk I mentioned the constancy of enzyme concentrations ; 

 the particular system I had in mind was the working muscle going from 

 rest to activity ; then the increase of metabolism is very great without, 

 of course, a change in the amounts of enzymes. I quite agree that 

 there are other circumstances where the amounts of enzymes increase. 



