The glutamate-glutamine cycle is not stoichiometric: Fates of glutamate in brain
The glutamate-glutamine cycle is not stoichiometric: Fates of glutamate in brain
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DOI：
10.1002/jnr.21444
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发表时间：
2007-11-15
影响因子：
4.2
通讯作者：
McKenna, Mary C.
中科院分区：
文献类型：
--
作者：
McKenna, Mary C.
虽然谷氨酸通常被认为是大脑中主要的兴奋性神经递质，但重要的是要注意谷氨酸在大脑中有许多其他命运，包括氧化为能量，掺入蛋白质，形成谷氨酰胺，γ-氨基丁酸（GABA）和谷胱甘肽。谷氨酸在脑细胞中的区室化是复杂的，并且受谷氨酸本身以及其他代谢物的存在和浓度的调节。星形胶质细胞和神经元都可以区分外源性谷氨酸和谷氨酰胺通过转氨酶内源性形成的谷氨酸。有证据表明，在神经元和星形胶质细胞内存在多个谷氨酸亚细胞区室，谷氨酸的碳骨架可以来自其他氨基酸和许多能量底物，包括葡萄糖、乳酸和3-羟基丁酸。星形胶质细胞和神经元都利用谷氨酸，尽管是细胞特异性的代谢命运。谷氨酸在神经元中容易由星形胶质细胞中合成的谷氨酰胺形成，释放到细胞外空间，并被神经元摄取。然而，谷氨酸-谷氨酰胺循环不是化学计量循环，而是一种开放途径，其与许多其他代谢途径在不同程度上相互作用，这取决于细胞的需求和优先级。(c)2007 Wiley-Liss，Inc.
Although glutamate is usually thought of as the major excitatory neurotransmitter in brain, it is important to note that glutamate has many other fates in brain, including oxidation for energy, incorporation into proteins, and formation of glutamine, gamma-aminobutyric acid (GABA), and glutathione. The compartmentation of glutamate in brain cells is complex and modulated by the presence and concentration of glutamate per se as well as by other metabolites. Both astrocytes and neurons distinguish between exogenous glutamate and glutamate formed endogenously from glutamine via glutaminase. There is evidence of multiple subcellular compartments of glutamate within both neurons and astrocytes, and the carbon skeleton of glutamate can be derived from other amino acids and many energy substrates including glucose, lactate, and 3-hydroxybutyrate. Both astrocytes and neurons utilize glutamate, albeit for cell-specific metabolic fates. Glutamate is readily formed in neurons from glutamine synthesized in astrocytes, released into the extracellular space, and taken up by neurons. However, the glutamate-glutamine cycle is not a stoichiometric cycle but rather an open pathway that interfaces with many other metabolic pathways to varying extents depending on cellular requirements and priorities. (c) 2007 Wiley-Liss, Inc.