Glutaminase and glutamine synthetase activities in human cirrhotic liver and hepatocellular carcinoma.
Glutamine synthetase and glutaminase activities in human cirrhotic liver tissues and hepatocellular carcinomas were determined for comparison with normal liver tissues. In hepatocellular carcinoma, glutamine synthetase activity was approximately one-third of that in normal liver, whereas no detectable change in the enzyme activity was observed in cirrhotic liver. Phosphate-dependent and phosphate-independent glutaminase activities were increased approximately 20-fold and 6-fold, respectively, both in the carcinoma and cirrhotic liver compared with those from normal liver, Oxypolarographic tests showed that the rate of glutamine oxidation in the tumor and cirrhotic liver mitochondria was about 5-fold higher than that in the liver mitochondria. The rate of glutamate oxidation in the liver mitochondria was comparable to that in the cirrhotic liver and tumor mitochondria. Glutamine oxidation was inhibited by prior incubation of the mitochondria with 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 and cirrhotic liver mitochondria to supply ATP. In the liver and cirrhotic liver mitochondria, glutamate was oxidized via the routes of transamination and deamination. On the other hand, glutamate oxidation was initiated preferentially via a transamination pathway in the tumor mitochondria.
Department of Measles Virus, National Institute of Health, Tokyo, Japan.
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Matsuno
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Goto
D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D005972:Glutaminase / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology; D008103:Liver Cirrhosis / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D010101:Oxygen Consumption
D005973:Glutamine; D005972:Glutaminase; D005974:Glutamate-Ammonia Ligase