A Comparison of Glucose Utilization by Mouse Liver and by the Transplantable Hepatocarcinoma

The following aspects of carbohydrate metabolism were compared in liver and in the transplantable hepatocarcinoma C954 carried by the C57-1eaden mouse strain: (a) glucose production from endogenous sources; (b) glucose-6-phosphatase and isomerase activities; (c) glycogen synthesis; (d) extent of glucose utilization for CO2, lactate, and fatty acid formation; (e) pathways of glucose catabolism; and (f) operation of the tricarboxylic acid cycle. Liver slices produced a large amount of glucose from endogenous sources. No such formation was detected in the experiments with the hepatocarcinoma slices. This inability of the tumor to form glucose from endogenous sources was associated with the absence of gucose-6-phosphatase in homogenates prepared from it. The presence of hexosephosphate isomerase was demonstrated in both tumor and liver. No glycogen synthesis from glucose was observed in slices of the hepatocarcinoma. The extent of utilization of glucose for lactate and fatty acid formation by liver and tumor slices was studied with various concentrations of labeled glucose in the medium. At all concentrations studied the recoveries of C 14 as lactate and fatty acids in the experiments with tumor slices surpassed those observed with liver. In host liver slices the yields of C1402, C14-1abeled fatty acids, and lactate-C 14 from g!ucose-!-C 1~ and -6-C 14 were approximately equal. In the hepatoearcinoma C9~ slices the C1402 yields from glucose-l-O 4 were ~-3 times those from glucose-6-C ~4. The recoveries of C14-1abeled fatty acids and lactate-C 14 from glucose-6-C 14 exceeded those from glucose-l-C ~4 in the experiments with the hepatocarcinoma. The participation of the hexosemonophosphate oxidative pathway in glucose metabolism of this tumor was estimated by two methods. A considerable portion of glucose catabolism in the tumor proceeded via this direct oxidative pathway. I t would appear that, in the liver of the tumor-bearing mouse, the Embden-Meyerhof scheme is by far the major pathway for con~ ersion of glucose carbon to fatty acids. Chromatographic-radioautographic analysis of water-soluble compounds derived from glucose breakdown by the slices of the hepatocarcinoma offers evidence for the operation of the tricarboxylic acid cycle in this neoplasm. Evidence suggestive of a defect in the conversion of glutamate to glutamine by the hepatocarcinoma is presented.