II CARBOHYDRATES AND LIPIDS 885 



''*C02 after incubation of mouse tumor slices with glucose- i-''*C or glucose-6- 

 '"•C in Krebs-Ringer phosphate. The CO2 from the labeled glucose is initially 

 more active from Cj than C^ if the oxidative pathway is in operation. Carbon atoms 

 I and 6 appear at equal rates if the glycolytic scheme is operative. The ratio RjR^ 

 (when i? = radioactivity as COj) was found to be 0.7 for mouse liver, i.i for dia- 

 phragm, 0.47 for mammary carcinoma, 0.35 for hepatoma, 0.69 for ovarian tumor 

 and 0.65 for sarcoma. From the lactic acid isolated from the medium it could be 

 calculated that approximately 70% of the glucose- i-''*C molecules giving rise to 

 the lactic acid has followed the oxidative pathway in mammary carcinoma and 

 50% in ovarian tumors and sarcoma. 



Wennere/fl/. (1956) employing glucose labeled with '"^C in all positions, in carbon' ^ 



or carbon^, estimated the pathway of respiration and glycolysis in solid and ascites 

 tumors. They reported that 77-94% of the glucose catabolized in tumors was 

 converted into lactic acid and the remainder into CO2. Most of the respiratory CO2 

 arose via the Embden-Meyerhof pathway and the citric cycle. Holzer et al. (1955) 

 also reported that cells of the Ehrlich ascites tumor metabolize glucose via the 

 Embden-Meyerhof scheme. Frvictose may also be directly phosphorylated to 

 fructose-6-phosphate and enter the pathway through fructose- 1,6-diphosphate. 

 The Embden-Meyerhof pathway is active in the glucose metabolism of normal 

 liver. In transplantable hepatocarcinoma in C57 mice the hexose monophosphate 

 shunt may account for 25-50% of the fatty acids and lactate derived from glucose 

 (Abraham et al., 1955, 1956). In contrast, normal rat or mouse mammary tissue 

 is characterized by a high hexosemonophosphate shunt activity, which is greatly 

 reduced in adenocarcinoma of the mammary gland. Tumor tissues never exceed 

 an aerobic oxidative rate of Q.o, 20-25 according to Reif ^/ al. (1953) in either the 

 malic or succinoxidase systems. However, the oxidative capacity of certain normal 

 tissues greatly exceeds that of tumors. These investigators developed a system for 

 aerobic glycolysis of fructose- 1,6-diphosphate by tissue homogenates. A gradation 

 of oxidative capacity was demonstrated from high values for normal to the lowest 

 range for tumor tissues. The addition of brilliant cresyl blue doubled the oxygen 

 uptake of tumors but did not affect the normal tissues, suggesting a limited DPN- 

 cytochrome c reductase in tumors. They also found that tumor homogenates 

 produced lactic acid from glucose. Brain homogenates carried out this reaction 

 anaerobically but other normal tissues were unable to produce lactic acid in the 

 absence of other substrates. 



Both normal and leukemic myeloid cells are characterized by high aerobic 

 glycolysis while lymphatic leukemic lymphocytes and blasts forms have low 

 aerobic glycolytic rates (Beck and Valentine, 1952, 1953; Beck, 1955). Leukemic 

 cells require more cytochrome c for a maximal uptake of oxygen than normal 

 cells. McKinney and Rundles (1956) have also noted that leukocytes from patients 

 with either chronic myelocytic or lymphatic leukemia produced less lactic acid 

 aerobically than anaerobically. The leukemic leukocytes produced less lactic acid 

 than normal leukocytes. From the findings of Steinberg et al. (1952) it would 

 appear that the oxidative capacity is low for all lymphoid tissues, normal or ma- 

 lignant. On a basis of oxidative activity these investigators could not distinguish 

 between normal and malignant lymphoid tissues. Kit (1956) incubated suspensions 



Literature p. gig 



