Glutamate metabolism in the brain focusing on astrocytes.
Glutamate metabolism in the brain focusing on astrocytes.
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DOI：
10.1007/978-3-319-08894-5_2
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发表时间：
2014
影响因子：
--
通讯作者：
McKenna MC
中科院分区：
文献类型：
--
作者：
Schousboe A;Scafidi S;Bak LK;Waagepetersen HS;McKenna MC
谷氨酸是GABA的前体物质，是脑内主要的兴奋性神经递质，其代谢非常复杂且高度区室化。这些神经递质池的维持严格依赖于星形胶质细胞中谷氨酰胺的从头合成，这需要回补酶丙酮酸羧化酶和谷氨酰胺合成酶。谷氨酸是直接从谷氨酰胺通过脱酰胺通过磷酸活化转氨酶，也产生氨的反应。谷氨酸通过三羧酸（TCA）循环连接碳水化合物和氨基酸代谢，以及在脑中的氮运输和氨稳态中起关键作用。星形胶质细胞终足的解剖学特化使这些细胞能够快速有效地从突触间隙中去除神经递质以维持稳态，并提供谷氨酰胺以补充谷氨酸能和GABA能神经元中的神经递质库。由于谷氨酸-谷氨酰胺循环是一个开放的循环，积极与其他途径的接口，从头合成的谷氨酰胺在星形胶质细胞有助于维持这个周期的运作。星形胶质细胞的微调生化专业化允许这些细胞通过动态调整其回补和糖酵解活性来响应神经传递的微妙变化，并调整相对于直接形成谷氨酰胺的能量氧化谷氨酸的量，以满足维持神经传递的需求。本章总结了星形胶质细胞在脑内谷氨酸能和GABA能神经传递中的重要和动态伙伴的证据。
Metabolism of glutamate, the main excitatory neurotransmitter and precursor of GABA, is exceedingly complex and highly compartmentalized in brain. Maintenance of these neurotransmitter pools is strictly dependent on the de novo synthesis of glutamine in astrocytes which requires both the anaplerotic enzyme pyruvate carboxylase and glutamine synthetase. Glutamate is formed directly from glutamine by deamidation via phosphate activated glutaminase a reaction that also yields ammonia. Glutamate plays key roles linking carbohydrate and amino acid metabolism via the tricarboxylic acid (TCA) cycle, as well as in nitrogen trafficking and ammonia homeostasis in brain. The anatomical specialization of astrocytic endfeet enables these cells to rapidly and efficiently remove neurotransmitters from the synaptic cleft to maintain homeostasis, and to provide glutamine to replenish neurotransmitter pools in both glutamatergic and GABAergic neurons. Since the glutamate-glutamine cycle is an open cycle that actively interfaces with other pathways, the de novo synthesis of glutamine in astrocytes helps to maintain the operation of this cycle. The fine-tuned biochemical specialization of astrocytes allows these cells to respond to subtle changes in neurotransmission by dynamically adjusting their anaplerotic and glycolytic activities, and adjusting the amount of glutamate oxidized for energy relative to direct formation of glutamine, to meet the demands for maintaining neurotransmission. This chapter summarizes the evidence that astrocytes are essential and dynamic partners in both glutamatergic and GABAergic neurotransmission in brain.