Histochemical evaluation of energy metabolism in rat glioma.
The key enzymes of oxidative phosphorylation and glycolysis were evaluated histochemically in rat-implanted C6 gliomas using spot densitometry. Hexokinase, the initial enzyme for the glycolysis pathway, was 40% higher within tumour than the contralateral cerebral cortex. A similar increase within tumours for 2-deoxyglucose was observed by autoradiography. Glucose-6-phosphate dehydrogenase (G6PDH), which is the first enzyme in the pentose phosphate pathway, shunting glucose towards nucleic acid synthesis, was more than 300% higher in gliomas compared with the normal cortex. In contrast, enzymes in the energy producing tricarboxylic acid cycle (succinate-, isocitrate-, and malate-dehydrogenase) and in the electron-transport system (cytochrome c oxidase) were significantly reduced in tumour (58% less than the contralateral cortex). Lactate dehydrogenase activity, which converts pyruvate to lactate, was 50% higher within tumour. Significant reductions of enzymatic activities also occurred in non-neoplastic tissue in ipsilateral hemisphere, with larger tumours. Some enzymes showed heterogeneous activity within tumours, especially G6PDH. These results suggest that: (1) energy production is more dependent on lactate production than on oxidative phosphorylation in C6 glioma, and (2) a significant part of the increased glucose utilization in glioma cells is due to increased activity of the pentose phosphate shunt for increased DNA synthesis, and not energy production.
Division of Neurosurgery, Jonsson Cancer Center, University of California Los Angeles School of Medicine 90024.
K
K
Ikezaki
K L
KL
Black
S G
SG
Conklin
D P
DP
Becker
D000818:Animals; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D004734:Energy Metabolism; D004798:Enzymes / Q000032:analysis; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006019:Glycolysis; D009363:Neoplasm Proteins / Q000032:analysis; D009368:Neoplasm Transplantation; D010085:Oxidative Phosphorylation; D051381:Rats; D014407:Tumor Cells, Cultured
D004798:Enzymes; D009363:Neoplasm Proteins