226 Discussion 



which aerobic glucose utilization is rapidly accelerated by a greater 

 availability of ATP in the cytoplasm. As more accurate data become 

 available on reaction velocity constants and enzyme concentrations, 

 this minimal hypothesis may be greatly further refined and may be 

 used to point the way to new experimental tests of theories on metabolic 

 control. 



Siekevitz: It has recently been found that the mitochondria cannot 

 store ATP (Siekevitz, P., and Potter, V. R. (1955). J. biol. Chem., 215, 

 237 ; Pressman, B. C. (1958). J. biol. Chem., 232, 947). During oxidative 

 phosphorylation it is made and it goes out, and it is not stored. 



Chance: Mitochondria isolated from the liver contain ATP, which 

 does not go directly to hexokinase ; apparently it is stored at a certain 

 point and is not available. 



Siekevitz: As more is made it is put out. 



Chance : They are isolated and are not the same as in the cell. 



Bartley : Dr. Racker, does the extra phosphate that is taken up when 

 you increase the external phosphate mix with the pool of internal 

 phosphate in the cell? 



Racker: The measurements of transport by ^^p determinations and by 

 chemical analysis of intracellular phosphates have been in reasonably 

 good agreement (making reasonable corrections, of course). The phos- 

 phate which is thus taken up must mix to some extent with the intra- 

 cellular pool of inorganic phosphate which is available for esterification. 

 The distribution of ^^p into the various organic phosphate fractions has 

 been explored and it seems that under our experimental conditions the 

 incorporation into phosphate esters is quite rapid. 



Bartley: If you use radioactive phosphate in the early stages, this 

 will give you the size of the eftective phosphate pool. 



Racker : Our kinetic studies of the early stages of phosphate transport 

 have not been too extensive but there are already indications that the 

 course of ATP labelling does not quite follow that of the intracellular 

 Pi. This type of experiment may give us some further clues to the 

 problem of compartmentation in the ascites tumour cells. 



Greville: I understand that the Pasteur elTect in tumour cells results 

 from interaction between respiring mitochondria and the glycolytic 

 system. Now in rabbit skeletal muscle, for instance, where there are 

 practically no mitochondria, the mitochondria can have very little 

 influence on the glycolysis. I wonder whether in the ascites tumour 

 cells and other tumour cells there is a low content of mitochondria, or 

 whether the mitochondria have a light load of respiratory enzymes; 

 either of these might account for the aerobic glycolysis. 



Racker: Is respiration really low? The Q02 of ascites tumour cells, 

 even according to Warburg, is 7, which is quite respectable. Weinhouse 

 has obtained even higher values. The question of whether tumour cells 

 have a large or small Pasteur effect seems to depend on the point of 

 view. Although Warburg has maintained that the relative Pasteur 

 effect as calculated on a percentage basis is smaller in tumour tissues, 

 Weinhouse has pointed out that the absolute Pasteur effect, which is 

 the amount of lactic acid suppressed, is actually even greater in tumour 



