e A SYMPOSIUM ON RESPIRATORY ENZYMES 



biased judgment I dare say that both cases are characterized by the 

 same numerical relationship— the oxidation quotient, which expresses 

 the ratio of the aerobic disappearance of splitting metabolism in 

 moles sugar to the oxidized sugar equivalents (12). Critics have 

 objected that under extreme conditions this number may range 

 from zero to infinite, but it is equally true, and more important, I 

 think, that under physiological conditions living cells exhibit quo- 

 tients between 3 and 6— approaching 6 more and more as the con- 

 ditions of temperature, oxygen pressure, nutritional state, and milieu 

 become optimal for the cells in question. The same preference for 

 the quotient of 6 was demonstrated by O. Warburg for different 

 warm-blooded tissues where the anaerobic glycolysis is high enough 

 to allow the calculation of the quotient (13). 



The original concept of a metabolic carbohydrate cycle involved 

 the assumption that in the stationary state the quotient results from 

 a continuous overlapping of anaerobic glycolysis and of oxidative 

 resynthesis of the cleavage products— the endothermic resynthesis 

 made possible by coupling with oxidation. Today it seems possible 

 to refine this scheme and to modify it somewhat without rejecting 

 the main argument. Indeed, in the past fifteen years a tremendous 

 amount of material has been collected to prove that the general 

 concept of these cycles in carbohydrate breakdown holds good, 

 that every oxidative step is coupled with an involuntary phosphoiy- 

 lation, and that the several intermediate stages of the anaerobic 

 breakdown can be reversed by means of the "energy-rich phosphate 

 bonds" (31) created in this way. 



On the other hand, the original concept of a single complete 

 cycle passing through the stage of lactic acid cannot be exactly 

 true for a very simple reason, which has become clear since 1933; 

 namely, that pyruvic acid is the necessary precursor of lactic acid in 

 glycolysis and of alcohol in yeast fermentation (14). Under anaerobic 

 conditions the reduction of pyruvic to lactic acid is compensated 

 for by the oxidation of phosphoglyceraldehyde to phosphoglyceric 

 acid. The latter, in turn, is decomposed via two intermediaries to 

 pyruvic acid (15). The hydrogen transfer proceeds in both directions 

 by the way of cozymase, the diphosphopyridine nucleotide of War- 

 burg. 



But if oxygen is present the dihydrocozymase can transfer its two 

 hydrogen atoms to oxygen instead of to pyruvic acid by a long chain 

 of oxidative catalysts : the pheohemin enzyme of Warburg, the three 

 cytochromes, and the flavinproteins; consequently the pyruvic acid 



