INTERMEDIATE CARBOHYDRATE METABOLISM 5 



(4) showed that specially treated, washed bacteria may lose the 

 power to oxidize sugar and other substrates, but retain the power 

 to oxidize lactic to pyruvic acid. Experiments on muscle lead to the 

 same conclusion. After a muscle is poisoned with iodoacetic acid the 

 formation of lactic acid is blocked; at the same time the respiratory 

 quotient drops to 0.7, and is not changed by the addition of sugar, 

 but is brought to 0.95 by the addition of lactic acid. Respiration is 

 increased, and oxygen consumption is essentially equivalent to the 

 disappearance of lactic acid (5). Similar results were obtained by 

 Krebs with respiration of brain and testis after poisoning with 

 iodoacetic acid (6). Since oxidation of sugar is completely checked, 

 no interpretation is possible except that lactic acid is directly oxi- 

 dized. 



But this is not necessarily the pathway of sugar oxidation in the 

 aerobic steady state. That independent ways of sugar oxidation 

 exist may be gathered from many observations, such as the rapid 

 oxidation of fructose in brain tissue, where, in contrast to glucose 

 (7), it does not give rise to anaerobic lactic acid. Furthermore, 

 Warburg and Christian showed that hexosemonophosphate can be 

 oxidized by the triphosphopyridine nucleotide in yeast extract to 

 phosphogluconic acid (8), and Lipmann demonstrated the complete 

 oxidation to carbon dioxide in this manner (9). 



On the other hand, the oxidation of sugar by way of pyruvic acid 

 is also firmly established, and in this case the steps up to the forma- 

 tion of the acid are identical in respiration and in anaerobic gly- 

 colysis. As was discovered by Peters (10), pyruvic acid accumulates 

 during oxidation of carbohydrate by cells and tissues in cases of 

 vitamin B^ deficiency, which means that lack of cocarboxylase 

 blocks the oxidative decarboxylation of pyruvic acid. Many other 

 findings, such as the similarity of the oxidation of pyruvic acid to 

 that of sugar in tissue pulps and extracts, point in the same direction, 

 namely, that sugar is oxidized via pyruvic acid (11). Thus several 

 pathways of sugar oxidation exist, the choice of which may depend 

 upon the special set of enzymes in different tissues and also upon 

 hormonal and other controlling influences. 



All this probably has some bearing on the relationship already 

 mentioned between oxidation and interference with the mechanism 

 of fermentation. I have mentioned before the two possible cases of 

 this relationship— the actual synthesis of split products to the initial 

 substance and the non-formation of the split products during the sta- 

 tionary state of respiration. Without fearing to be accused of a 



