REGULATORY MECHANISMS IN ENERGY METABOLISM 151 



dinitiophenol stimulated lactic acid production auacrobically in frog 

 muscle. Recently similar results were obtained in ascites cells 

 ( Slechta and Bentley, 1960) . Windisch and Heumann ( 1960) found 

 that levels of dinitrophenol which inhibited the Pasteur reaction 

 stopped veast from growing altogether. Yet all these effects cannot 

 be explained solelv by the mere activation of ATP-ase. First of all, 

 for at least two functions ATP is readily available (cf. Table 5-2). 

 Secondlv, it is even doubtful whether ATP-ase activation by dinitro- 

 phenol actually exists in vivo. It seems reasonable to assert that the 

 evidence of dinitrophenol reversal of the Pasteur effect in itself is 

 not sufficient to claim ATP availability as the underlying cause. 



Increased and lowered ADP availability could do the same as 

 inorganic phosphate. However, again compartmentation will then 

 have to be involved, since the ADP levels do not strikingly differ 

 from the anaerobic to aerobic state (Lynen et al, 1959). Further- 

 more, as has been mentioned before, with normally respiring sys- 

 tems, ADP lack, just as phosphate lack, would not lower glucose 

 phosphorylation. 



Competition of Respiration and Glycolysis: DPNH Formation. 



The suggestion by Ball (1939) of competition for reduced coen- 

 zymes between glycolysis and oxidation needs some further inves- 

 tigation. It is generally discredited as an explanation for the Pasteur 

 effect. However, DPN is definitely compartmentized. In whole 

 cells it is difficult to distinguish between non-mitochondrial and 

 mitochondrial DPN, so that studies involving pyridine nucleotide 

 levels require homogenization of the tissue. 



In the whole animal the cytoplasmic DPN DPNH ratio is about 

 5-7/1 ( Clock and McLean, 1956; Jacobson and Kaplan, 1957 ) . This 

 is reflected in a lactate/pyruvate ratio of about 20/1 (Biicher and 

 Klingenberg, 1958).'' When one homogenizes liver and brain and 

 incubates it with glucose or fructose diphosphate, the lactate/pyru- 

 vate ratio drops to about unity ( van Eys and Warnock, 1959 ) . This 

 is also found in brain supernatant (Aisenberg et al, 1957). If this 

 pyruvate level still reflects DPN/DPNH ratios, the level of DPNH 

 must be negligible. This is a serious departure from the normal 

 situation. Surprisingly enough, addition of an ATP acceptor system 

 lowers this pyruvate level to the usual in vivo concentration (van 



5 Tliis is not a thermodynamic equilibrium with free DPN and DPNH. However, 

 most pyridine nucleotides are bound to dehydrogenases, thus giving a considerably 

 different potential to the DPN/DPNH couple. 



