Matsuno T, Goto I
Department of Measles Virus, National Institute of Health, Tokyo, Japan.
Cancer Res. 1992 Mar 1;52(5):1192-4.
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.
测定了人类肝硬化肝组织和肝细胞癌中的谷氨酰胺合成酶和谷氨酰胺酶活性，以便与正常肝组织进行比较。在肝细胞癌中，谷氨酰胺合成酶活性约为正常肝脏的三分之一，而在肝硬化肝脏中未观察到该酶活性有可检测到的变化。与正常肝脏相比，癌组织和肝硬化肝脏中依赖磷酸盐和不依赖磷酸盐的谷氨酰胺酶活性分别增加了约20倍和6倍。极谱氧测定试验表明，肿瘤和肝硬化肝脏线粒体中谷氨酰胺氧化速率比肝脏线粒体中的高约5倍。肝脏线粒体中谷氨酸氧化速率与肝硬化肝脏和肿瘤线粒体中的相当。线粒体预先与6-重氮-5-氧代-L-正亮氨酸孵育可抑制线粒体谷氨酰胺酶，从而抑制谷氨酰胺氧化。这些结果表明，谷氨酰胺水解产物谷氨酸在肿瘤和肝硬化肝脏线粒体中被分解代谢以提供ATP。在肝脏和肝硬化肝脏线粒体中，谷氨酸通过转氨和脱氨途径被氧化。另一方面，在肿瘤线粒体中，谷氨酸氧化优先通过转氨途径启动。
