Schreibmayer W, Schaur R J, Tillian H M, Schauenstein E, Hagmüller K
J Cancer Res Clin Oncol. 1980;97(2):137-44. doi: 10.1007/BF00409899.
To elucidate the origin of increased concentrations of alpha-ketoglutarate (KG) in tumor bearers the tissue distribution of KG together with the related metabolites citrate, succinate, malate, and glutamate was determined in tumor, liver, gastrocnemius muscle, and blood of rats bearing the solid Yoshida sarcoma and of tumor-free rats. The sum of these metabolites was significantly increased in host liver and blood, respectively, compared with the corresponding tissues of normal rats. Among single metabolites glutamate and malate were significantly increased in host liver. The absolute concentrations were highest in host liver with the exception of KG, which was highest in the tumor. This was taken as indicative for the tumor as the prime source of increased KG in blood of tumor-bearers. No significant metabolic deviations were found in gastrocnemius muscle. The concentration of KG in this muscle of both normal and host animals correlated significantly with that of glutamate. In the tumor the concentration of KG correlated significantly with that of citrate plus succinate plus malate. This type of correlation was absent in liver and muscle of both normal and host animals. Moreover, no correlation existed between KG and glutamate either in liver or in tumor. It was suggested that the metabolic flux through the citric cycle determines the concentration of KG in the tumor.
为阐明肿瘤宿主中α-酮戊二酸（KG）浓度升高的来源，测定了携带实体吉田肉瘤的大鼠及无瘤大鼠的肿瘤、肝脏、腓肠肌和血液中KG以及相关代谢物柠檬酸、琥珀酸、苹果酸和谷氨酸的组织分布。与正常大鼠的相应组织相比，这些代谢物的总和在宿主肝脏和血液中分别显著增加。在单一代谢物中，宿主肝脏中的谷氨酸和苹果酸显著增加。除KG外，绝对浓度在宿主肝脏中最高，而KG在肿瘤中最高。这被认为表明肿瘤是肿瘤宿主血液中KG增加的主要来源。在腓肠肌中未发现明显的代谢偏差。正常动物和宿主动物该肌肉中KG的浓度与谷氨酸的浓度显著相关。在肿瘤中，KG的浓度与柠檬酸+琥珀酸+苹果酸的浓度显著相关。正常动物和宿主动物的肝脏和肌肉中均不存在这种类型的相关性。此外，肝脏或肿瘤中KG与谷氨酸之间均不存在相关性。有人提出，通过柠檬酸循环的代谢通量决定了肿瘤中KG的浓度。
