4 A SYMPOSIUM ON RESPIRATORY ENZYMES 



fermentation and respiration remained for a long time a subject of 

 speculation, and even now many a question is unanswered. How- 

 ever, I should like to follow this latter trend of ideas a little more in 

 detail. 



PfeflFer and Pfliiger, following Pasteur, held a rather simple view 

 of this relationship: the first step of respiration was assumed to be 

 always anaerobic. If no oxygen is present, the products of anaerobic 

 cleavage accumulate: alcohol in yeast and higher plants, lactic acid 

 in the tissues of higher animals and in some bacteria. But if oxygen 

 is present, these products are oxidized to carbon dioxide and water. 



That this concept required modification became apparent twenty 

 years ago from studies of metabolism of muscle. In 1907 Fletcher and 

 Hopkins (1) showed that under anaerobic conditions frog muscles 

 formed lactic acid steadily during both activity and rest, and that 

 this lactic acid disappeared when oxygen was admitted. Parnas (2), 

 working some years later in the same Cambridge laboratory, claimed 

 to have found that this disappearance was a complete oxidation, thus 

 apparently confirming the views of Pfeffer and Pfliiger. In 1920, 

 because of the controversial state of this question, I repeated the 

 experiments of Parnas, avoiding especially all kinds of irritation or 

 injury of the muscles which would lead to extra-consumption of 

 oxygen (3). Under these conditions much more lactic acid disap- 

 peared in oxygen than could be accounted for by oxidation, and the 

 lactic acid unaccounted for was reconverted into carbohydrate. This 

 was true for the lactic acid formed during activity as well as for that 

 formed during rest. Similarly, it was shown that in equal periods of 

 rest much more lactic acid was formed anaerobically than could be 

 burnt aerobically by the resting respiration. Indeed, the amount of 

 oxygen which failed to be used in a period of anaerobiosis was about 

 the same as the excess consumed after that period. This oxygen was 

 suflBcient only to oxidize from a quarter to a sixth of the lactic acid 

 which disappeared. 



These facts, which are independent of special interpretations, are 

 sufficient to invalidate the original theory of Pfeffer and Pfliiger in 

 that they show that the oxidative removal of fermentation products 

 is not necessarily identical with the oxidation of these products. But 

 we can pose the more limited question whether the oxidation on the 

 whole attacks the end products of anaerobic breakdown. With 

 respect to lactic acid formed in a preceding anaerobic period, we 

 must surely answer in the affirmative. We know that lactic acid is 

 easily oxidized by way of pyruvic acid. For example, Barron et al. 



