884 METABOLISMOFTHECANCERCELL 12 



synthesis and that no decisive importance may be attached to the glycolytic mecha- 

 nism. 



It would appear that the glycolytic activity does play an important role in 

 malignant tissue metabolism. While Warburg and his colleagues still favor the 

 hypothesis of a faulty or impaired respiration, the overall effect may be controlled 

 by several factors. Since Warburg's original observations, our knowledge of the 

 respiratory process has been greatly increased with the advances made in electron 

 transport mechanisms, phosphorylation and in the further establishment of the 

 cycles involved in the oxidation of glucose and fatty acids (see Chapter i). Burk 

 and Woods (1956) are of the opinion that the impaired respiration of tumors may 

 involve any or all of the following : ( i ) a high ratio of glycolysis to respiration, 

 (2) a low absolute value for Oj consumption, (3) a deficient or uncoupled respi- 

 ration, (4) a low paraphenylenediamine oxidative response. 



Weinhouse (1955, 1956) in referring to Warburg's concept of a disturbed 

 respiration in tumor tissues believes that it would have been more accurate to 

 state that the anaerobic glycolysis of tumor slices is sufficiently high that a normal 

 respiration and a normal Pasteur effect are incapable of eliminating it. This, 

 according to W^einhouse would place the emphasis on the high glycolytic rate of 

 tumors rather than on the respiration or the Pasteur effect in the neoplastic cells, 

 A similar view has also been taken by Schmidt (1955). Weinhouse (1955) in 

 reviewing the work of LePage (1948, 1950) agrees that the Embden-Meyerhof 

 scheme of phosphorylative glycolysis and all of the phosphorylated intermediates 

 found in normal tissues are present in many primary as well as in transplanted 

 tumors. Weinhouse states "a highly significant feature of LePage's results is that 

 potential rates of glycolysis of normal tissues are as great as, or greater than, those 

 of tumor tissues, and that the low rate of glycolysis displayed by normal tissue 

 slices are not due to lack of enzymes for the reactions involved". 



There is some evidence to suggest that the high aerobic glycolysis of tumors 

 may have its origin in the pathways of electron transport. The following values 

 are reported for the comparative activities of oxidized and reduced diphospho- 

 pyridine nucleotides in normal and neoplastic tissues (Weinhouse, 1955). 



Oxidized diphosphopyridine Reduced DPJV 



nucleotide (DPjV) 



Normal tissue range 102-630 16-264 



Neoplastic tissue range 89-297 0-61 



Also, there has been some indication of a relative deficiency of cytochrome c 

 and cytochrome oxidase in tumor tissues. Chance and Castor (1952) employing 

 spectrophotometric methods studied ascites tumor cells by measuring the optical 

 density of the cytochrome a, b, c, and sl^ when respiration was stopped by oxygen 

 exhaustion. Their findings indicated that the cytochrome oxidase activity of the 

 neoplastic cells was within the ranges for normal cells. Many investigators have 

 established that glucose is metabolized via the Embden-Meyerhof scheme in 

 malignant tissues. Emmelot and associates (1955) compared the ^'*C recoveries in 



