Department of Clinical Pharmacology, College of Basic Medical Sciences, China Medical University, No. 92 Beier Road, Heping District, Shenyang, PR China.
Magn Reson Imaging. 2011 Dec;29(10):1319-29. doi: 10.1016/j.mri.2011.04.013. Epub 2011 Aug 5.
Glutamate plays a double role in (13)C-nuclear magnetic resonance (NMR) spectroscopic determination of glucose metabolism in the brain. Bidirectional exchange between initially unlabeled glutamate and labeled α-ketoglutarate, formed from pyruvate via pyruvate dehydrogenase (PDH), indicates the rate of energy metabolism in the tricarboxylic acid (V(TCA)) cycle in neurons (V(PDH, n)) and, with additional computation, also in astrocytes (V(PDH, g)), as confirmed using the astrocyte-specific substrate [(13)C]acetate. Formation of new molecules of glutamate during increased glutamatergic activity occurs only in astrocytes by combined pyruvate carboxylase (V(PC)) and astrocytic PDH activity. V(PDH, g) accounts for ~15% of total pyruvate metabolism in the brain cortex, and V(PC) accounts for another ~10%. Since both PDH-generated and PC-generated pyruvates are needed for glutamate synthesis, ~20/25 (80%) of astrocytic pyruvate metabolism proceed via glutamate formation. Net transmitter glutamate [γ-aminobutyric acid (GABA)] formation requires transfer of newly synthesized α-ketoglutarate to the astrocytic cytosol, α-ketoglutarate transamination to glutamate, amidation to glutamine, glutamine transfer to neurons, its hydrolysis to glutamate and glutamate release (or GABA formation). Glutamate-glutamine cycling, measured as glutamine synthesis rate (V(cycle)), also transfers previously released glutamate/GABA to neurons after an initial astrocytic accumulation and measures predominantly glutamate signaling. An empirically established ~1/1 ratio between glucose metabolism and V(cycle) may reflect glucose utilization associated with oxidation/reduction processes during glutamate production, which together with associated transamination processes are balanced by subsequent glutamate oxidation after cessation of increased signaling activity. Astrocytic glutamate formation and subsequent oxidative metabolism provide large amounts of adenosine triphosphate used for accumulation from extracellular clefts of neuronally released K(+) and glutamate and for cytosolic Ca(2+) homeostasis.
谷氨酸在（13）C- 核磁共振（NMR）光谱测定大脑葡萄糖代谢中具有双重作用。最初未标记的谷氨酸与通过丙酮酸脱氢酶（PDH）形成的标记的α-酮戊二酸之间的双向交换，指示神经元三羧酸（V（TCA））循环中的能量代谢率（V（PDH，n）），并通过额外的计算，还指示星形胶质细胞中的能量代谢率（V（PDH，g）），这通过使用星形胶质细胞特异性底物[（13）C]乙酸得到证实。在谷氨酸能活性增加期间，新的谷氨酸分子的形成仅在星形胶质细胞中通过丙酮酸羧化酶（V（PC））和星形胶质细胞 PDH 活性发生。V（PDH，g）占大脑皮层总丙酮酸代谢的15％，V（PC）占另外10％。由于 PDH 生成和 PC 生成的丙酮酸都用于谷氨酸合成，因此20/25（80％）的星形胶质细胞丙酮酸代谢通过谷氨酸形成进行。净递质谷氨酸[γ-氨基丁酸（GABA）]的形成需要将新合成的α-酮戊二酸转移到星形胶质细胞质溶胶中，α-酮戊二酸转氨酶转化为谷氨酸，酰胺化为谷氨酰胺，谷氨酰胺转移到神经元，其水解为谷氨酸并释放谷氨酸（或 GABA 形成）。谷氨酸-谷氨酰胺循环，作为谷氨酰胺合成率（V（循环））进行测量，也将先前释放的谷氨酸/GABA 转移到神经元，在最初的星形胶质细胞积累之后，并主要测量谷氨酸信号。葡萄糖代谢与 V（循环）之间建立的经验上的1/1 比例可能反映了与谷氨酸产生过程中的氧化/还原过程相关的葡萄糖利用，这些过程与相关的转氨过程一起，在增加的信号传递活动停止后，通过随后的谷氨酸氧化来平衡。星形胶质细胞谷氨酸的形成和随后的氧化代谢提供大量的三磷酸腺苷，用于从神经元释放的 K+和谷氨酸的细胞外裂口中积累，以及用于细胞质 Ca2+稳态。
