II CARBOHYDRATES AND LIPIDS 89 1 



Addition of glucose resulted in a shift towards lactate while addition of glutamate 

 increased the labeling of adenine. 



The findings of Busch and colleagues point up the fact that neoplastic tissues 

 are more or less characterized by a uniform but not an entirely unique metabolism. 

 Lactate is readily formed from pyruvate, especially in the presence of an increased 

 glucose concentration. The lactate formed is only slowly converted into other 

 metabolites. Several of the normal tissues have the capacity to convert pyruvate 

 into lactate, amino acids, or adenine, depending somewhat on the tissue involved 

 or the presence of other substrates. This would suggest that respiratory enzyme 

 balances as proposed by Potter may be the deciding factor in meeting the needs 

 of the particular tissue. Tumor tissues may depend upon their glycolytic pattern 

 to provide the energy and the metabolites that are required for mitotic division 

 and rapid growth. The significance of the high aerobic, anaerobic glycolysis and 

 the formation of relatively large qviantities of lactate during the growth of neoplas- 

 tic tissues is not entirely clear at this time. 



(d) Phosphorylation 



The available evidence would indicate that tumors are capable of obtaining 

 energy from the phosphorylative reactions associated with the various stages of 

 oxidation within the citric acid cycle. Under carefully controlled conditions, 

 Kielley (1952) demonstrated that tumor mitochondrial preparations do have the 

 capacity to readily synthesize ATP during the oxidation of a-ketoglutarate and 

 succinate. The question has been posed by Weinhouse (1955) as to whether the 

 differences in glycolytic metabolism between normal and tumor tissues may 

 occur at the hexokinase level where ATP and glucose react to give glucose-6- 

 phosphate. There is no definite evidence that would provide an answer to this 

 proposal. Morelli et al. (1953) in studying aerobic and anaerobic phosphorylation 

 in leukemic leucocytes did not detect any significant differences in the inorganic 

 phosphate between normal and leukemic cells. The level of phosphate was de- 

 creased and the lactic acid increased in the blood of cancer patients injected with 

 fructose (Reymond and Wild, 1953). In mouse mammary tumors and in rat hepa- 

 toma the phosphorylase, according to Goranson et al. (1954), was inactive without 

 the addition of adenylic acid. With added adenylic acid no significant differences 

 were found between the phosphorylase in the tumors or in normal liver. 



Glucose-6-phosphate and 6-phosphogluconate dehydrogenase activities were 

 determined by Glock and McLean ( 1 954) in several experimentally induced and 

 also spontaneous tumors. These enzyme activities were highest in lymphomas and 

 lowest in sarcomas. However, the activities fell within the normal range. W'eber 

 and Cantero (1955) reported that the glucose-6-phosphatase activity was lower 

 in fetal liver and in hepatoma than in normal or regenerating liver. Phosphogluco- 

 mutase was found to be absent in the NovikofT hepatoma (Weber and Cantero, 

 1956). Glucose-6-phosphate dehydrogenase was increased in the hepatoma. 

 Schlief and Schmidt (1955) reported that hexokinase and aldolase of mouse 

 ascites tumors were independent of the rate of growth of the tumors. Adenosine- 

 triphosphatase, however, was considerably increased in the rapidly growing 

 tumors. It has been previously reported that the ATPase activities of various nor- 



Literature p. gig 



