Glutamate and glutamine metabolism and compartmentation in astrocytes.
Glutamate and glutamine metabolism and compartmentation in astrocytes.
复制标题
星形胶质细胞中的谷氨酸和谷氨酰胺代谢和区室。
作者：
A. Schousboe;N. Westergaard;U. Sonnewald;S. Petersen;R. Huang;L. Peng;L. Hertz
谷氨酸和谷氨酰胺在培养的小鼠大脑皮层星形胶质细胞的代谢进行了研究，使用放射性标记（14 C）的氨基酸或13 C-标记的氨基酸结合NMR光谱的细胞提取物和冻干孵育介质。使用[U-13 C]谷氨酸盐，已经表明在星形胶质细胞中，外源性提供的谷氨酸盐主要（70%）通过三羧酸（TCA）循环氧化代谢，并在较小程度上（30%）直接代谢为谷氨酰胺。在TCA循环中代谢的谷氨酸在很大程度上以乳酸盐的形式回收，这表明星形胶质细胞特异性酶苹果酸酶具有功能活性。与[U-14 C]谷氨酰胺孵育导致谷氨酸的比放射性高于谷氨酰胺。还可以表明，谷氨酸和谷氨酰胺的代谢与天冬氨酸和丙氨酸不同。这些结果结合在一起强烈表明，谷氨酸/谷氨酰胺代谢星形胶质细胞是区室化的，并提出了这些氨基酸的多个细胞质和线粒体隔室的模型。
Metabolism of glutamate and glutamine in cultured mouse cerebral cortical astrocytes has been investigated using either radioactively labelled (14C) amino acids or 13C-labelled amino acids combined with NMR spectroscopy of cell extracts and lyophilyzed incubation media. Using [U-13C]glutamate it has been shown that in astrocytes exogenously supplied glutamate is primarily (70%) metabolized oxidatively through the tricarboxylic acid (TCA) cycle and to a lesser extent (30%) directly to glutamine. Glutamate metabolized in the TCA cycle is to a large extent recovered as lactate showing that the astrocyte-specific enzyme, malic enzyme is functionally active. Incubation with [U-14C]glutamine led to a higher specific radioactivity in glutamate than in glutamine. It could also be shown that glutamate and glutamine were metabolized differently to aspartate and alanine. These results taken together strongly suggest that glutamate/glutamine metabolism in astrocytes is compartmentalized and a model with multiple cytoplasmic and mitochondrial compartments of these amino acids is proposed.