Compartmentation of brain glutamate metabolism in neurons and glia
Compartmentation of brain glutamate metabolism in neurons and glia
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DOI：
10.1093/jn/130.4.1026s
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发表时间：
2000-04-01
影响因子：
4.2
通讯作者：
Yudkoff, M
中科院分区：
文献类型：
--
作者：
Daikhin, Y;Yudkoff, M
突触内[谷氨酸]必须保持较低水平，以便在释放递质谷氨酸后使信噪比最大化。这是通过星形胶质细胞快速摄取谷氨酸来实现的，星形胶质细胞将谷氨酸转化为谷氨酰胺。后者然后被释放到神经元，神经元通过线粒体谷氨酰胺酶形成用于神经传递的谷氨酸。这种代谢区室化模式称为“谷氨酸-谷氨酰胺循环”。“这个模型受到以下两个重要条件的限制：1）大脑通过天冬氨酸转氨酶强烈氧化谷氨酸; 2）因为几乎没有谷氨酸从血液进入大脑，它必须在中枢神经系统（CNS）中合成。谷氨酸碳的主要来源是葡萄糖，谷氨酸氮的主要来源是支链氨基酸，它们以气态方式转运到中枢神经系统中。这种安排实现了以下目的：1）维持低的外部[谷氨酸]，从而使去极化时的信噪比最大化; 2）补充神经元谷氨酸库; 3）以非神经活性形式通过细胞外液“运输”谷氨酸（谷氨酰胺）; 4）从血液中输入氨基，从而维持脑氮稳态;和5）谷氨酸/谷氨酰胺的氧化，这是一种在调节脑谷氨酸、天冬氨酸和γ-氨基丁酸方面赋予额外水平的控制的过程。
Intrasynaptic [glutamate] must be kept low in order to maximize the signal-to-noise ratio after the release of transmitter glutamate, This is accomplished by rapid uptake of glutamate into astrocytes, which convert glutamate into glutamine. The latter then is released to neurons, which, via mitochondrial glutaminase, form the glutamate that is used for neurotransmission. This pattern of metabolic compartmentation is the "glutamate-glutamine cycle." This model is subject to the following two important qualifications: 1) brain avidly oxidizes glutamate via aspartate aminotransferase; and 2) because almost no glutamate crosses from blood to brain, it must be synthesized in the central nervous system (CNS). The primary source of glutamate carbon is glucose, and a major source of glutamate nitrogen is the branched-chain amino acids, which are transported vapidly into the CNS. This arrangement accomplishes the following: 1) maintenance of low external [glutamate], thereby maximizing signal-to-noise ratio upon depolarization; 2) the replenishing of the neuronal glutamate pool; 3) the "trafficking" of glutamate through the extracellular fluid In a nonneuroactive form (glutamine); 4) the importation of amino groups from blood, thus maintaining brain nitrogen homeostasis; and 5) the oxidation of glutamate/glutamine, a process that confers an additional level of control in terms of the regulation of brain glutamate, aspartate and gamma-aminobutyric acid.