Glutamine synthetase and glutaminase activities in various hepatoma cells.
Glutamine synthetase and glutaminase activities in a series of hepatoma cells of human and rat origins were determined for comparison with normal liver tissues. Marked decrease in glutamine synthetase activity was observed in the tumor cells. Phosphate-dependent and phosphate-independent glutaminase activities were increased compared with those from normal liver tissues. Well coupled mitochondria were isolated from HuH 13 line of human hepatoma cells and human liver. Oxypolarographic tests showed that glutamine oxidation was prominent in the tumor mitochondria, while mitochondria from the liver showed a feeble glutamine oxidation. Glutamine oxidation was inhibited by prior incubation of the mitochondria with DON (6-diazo-5-oxo-L-norleucine), which inhibited mitochondrial glutaminase. These results indicate that the product of glutamine hydrolysis, glutamate, is catabolized in the tumor mitochondria to supply ATP.
Matsuno
T
T
Department of Measles Virus, National Institute of Health, Tokyo, Japan.
Hirai
H
H
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D005972:Glutaminase / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D051381:Rats
D005972:Glutaminase; D005974:Glutamate-Ammonia Ligase