148 CONTROL MECHANISMS IN CELLULAR PROCESSES 



rious discrepancy. It is hard to assume that addition of liver mito- 

 chondria to brain restores conditions that are lost by ordinary brain 

 homogenization. Therefore the in vivo applicability of the system 

 as used by Potter is doubtful indeed. The question of inhibition of 

 glucose utilization by substrate inhil^ition is further complicated by 

 the fact that yeast hexokinase is rather insensitive to substrate inhibi- 

 tion; yet yeast shows a normal Pasteur effect. 



Competition of Respiration and Glycolysis: Phosphate Metab- 

 olism. At the present time, the key to the Pasteur effect is most 

 generally sought in the oxidative and glycolytic phosphorylative 

 processes. This was first proposed by Johnson ( 1941 ) and independ- 

 ently by Lynen ( 1941 ) . Theories along these lines have the advan- 

 tage of being teleologically satisfying. Lynen's experiments clearly 

 indicate that glucose assimilation is the same aerobically and anaer- 

 obically (Lynen, 1957). Therefore, since the rate of regeneration 

 of ATP is manv times slower anaerobicallv than it is aerobicallv, 

 given an identical need, glycolysis must be faster anaerobically than 

 aerobically. The difficultv lies in identifying the actual pacemaker 

 in the triad ATP, ADP, inorganic phosphate. Both ADP and in- 

 organic phosphate can limit the rate of glycolysis. There is ample 

 evidence that large amounts of inorganic phosphate can alleviate 

 the Pasteur effect (Kvamme, 1958d; Wu and Racker, 1959b) . How- 

 ever, the changes in inorganic phosphate in the transition from 

 anaerobic to aerobic conditions are small (Lynen et al., 1959). Wu 

 and Racker (1959b) also noted that there was a discrepancy be- 

 tween the rate of glycolysis and the inorganic phosphate concentra- 

 tion. There are ways out of this difficulty: either phosphate is com- 

 partmentalized or phosphate measurements include labile phosphate 

 esters. 



An additional point which must be considered is that lack of 

 phosphate or lack of ADP may limit glycolysis but will not neces- 

 sarily limit glucose uptake if the level is sufficiently high for normal 

 respiration. In fact, reconstructed systems, as studied by Gatt and 

 Racker (1959a, 1959b), demonstrate this phenomenon. The addi- 

 tion of mitochondria to purified glycolytic enzymes blocks lactate 

 formation but maintains glucose phosphorylation. When adenine 

 nucleotides are hmiting, this can be changed by appropriate selec- 

 tion of their concentrations, but this observation re-emphasizes the 

 fact that limiting ADP alone will not impair glucose utilization. 



