Discussion 105 



the older experiments that the sugar content of most tissues is indeed 

 extremely low, of the order of 10-15 mg. per cent in the case of muscle, 

 brain and testicle. Sugar was taken to diffuse very readily into cells, but 

 this low concentration indicates that there is some barrier at the cell 

 surface and that transport into the cell is something "active". Perhaps 

 phosphorylated sugar only is transported into the cell, in which case the 

 hexokinase would be required to be in the surface of the cell; but this is 

 merely an idea. The point I made is that the hexokinase reaction itself 

 or a step preceding it, dealing with the entry of sugar into the cell, is the 

 reaction which initiates the degradation of sugar in the cell. 



Haddow: We have become very interested in the properties of the cell 

 surface in malignant cells and homologous normal cells. There are 

 charge differences. 



Zamecnik: Prof. Krebs, would you comment on the reactions leading 

 toward synthesis of nucleic acid as possible rate-limiting steps ? We are 

 just beginning to get a more complete description of the series of 

 reactions leading to nucleic acid synthesis, and I wonder if they may not 

 be as likely a site as the steady-state conditions involved in glycolysis 

 and oxidative phosphorylation. 



Krebs: There must, of course, be rate-limiting reactions for many 

 processes. What I have discussed in detail, because we have information 

 on them, are the energy-giving reactions. The synthesis of nucleic acids is 

 one of the processes dependent on energy supply. But its rate certainly 

 does not depend merely on how much ATP is available. There must be 

 some other mechanisms which control it. I have no idea of what these 

 might be. I certainly agree that every complex synthesis must have a 

 component which determines its rate. I should emphasize again the 

 principle that there may be some reactions which are of less interest, if 

 you study the effect of extraneous agents, than others which are more 

 relevant because they determine the overall rate. 



Lajtha: In connection with that point we have found that uracil 

 deoxyriboside is readily methylated and gets into DNA thymine with 

 relatively low concentration of inorganic phosphate in the medium ; but 

 cytosine deoxyriboside needs a high concentration of inorganic phos- 

 phate in the medium to do the same. Could that inorganic phosphate 

 be already an energy-giving substance? 



Krebs: I don't visualize any direct connection, but I must make it 

 clear that the ideas which I have put forward cannot explain everything, 

 they are merely meant to give some guidance in experimentation. They 

 do not throw light on why you need a high concentration of phosphate 

 in one case and not in another. 



Cohn: In connection with the question on the biosynthesis of the 

 nucleic acids, it is quite clear now that they begin with rather small 

 molecules, e.g. with hexoses, trioses and dioses to build the ribose and 

 deoxyribose moieties, formate to fill in the place in the purine ring as 

 well as to add the methyl group, glycine, etc. So it seems to me that any 

 influence upon such steps as these must be reflected in the amounts of 

 substrates available for the build-up of nucleic acids, and thereby have 

 some effect, however remote. 



