Is there in vivo evidence for amino acid shuttles carrying ammonia from neurons to astrocytes?
Is there in vivo evidence for amino acid shuttles carrying ammonia from neurons to astrocytes?
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DOI：
10.1007/s11064-012-0898-7
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发表时间：
2012-11
影响因子：
4.4
通讯作者：
Behar, Kevin L.
中科院分区：
文献类型：
--
作者：
Rothman, Douglas L.;De Feyter, Henk M.;Maciejewski, Paul K.;Behar, Kevin L.
体内谷氨酸/谷氨酰胺循环的高通量对磷酸激活的谷氨酰胺酶释放的氨从神经元返回到星形胶质细胞以维持氮平衡提出了强烈的要求。在这篇文章中，我们综述了在谷氨酸/谷氨酰胺循环中平衡神经元和星形胶质细胞之间氮流的几种氨基酸穿梭。所有这些循环都依赖于谷氨酸脱氢酶的方向性，在神经元中催化还原谷氨酸合成(正向反应)以捕获磷酸激活的谷氨酰胺酶释放的氨，同时催化星形胶质细胞中的谷氨酸氧化脱氨(反向反应)释放氨以合成谷氨酰胺。对使用13N和15N标记的氨和亮氨酸的大鼠体内实验结果的重新分析表明，神经元和星形胶质细胞之间丙氨酸/乳酸或支链氨基酸/支链氨基酸转氨酶穿梭的最大流量大约比维持谷氨酸/谷氨酰胺循环所需的从神经元到星形胶质细胞的氨转移所需的氨转移流量低3-5倍。然而，在大鼠大脑中，谷氨酸脱氢酶的总氨固定率和支链氨基酸转氨酶的总活性都足以支持支链氨基酸/支链酮酸穿梭，这将支持星形胶质细胞中谷氨酰胺的从头合成，以取代被氧化的神经递质谷氨酸的∼20%。谷氨酸和三羧酸循环中间体充当氮穿梭的混合循环可以支持谷氨酸神经递质循环中较高比例的氮素需求。迄今为止在动物身上进行的所有体内研究的局限性是，没有一项研究表明，用于谷氨酰胺合成的氮以游离氨的形式或通过氨基酸从神经元转移到星形胶质细胞。未来的工作将需要，也许使用选择性标记神经元中的氮的方法，以最终确定体内氨基酸氮穿梭的速率及其与谷氨酸/谷氨酰胺循环的偶联。
The high in vivo flux of the glutamate/glutamine cycle puts a strong demand on the return of ammonia released by phosphate activated glutaminase from the neurons to the astrocytes in order to maintain nitrogen balance. In this paper we review several amino acid shuttles that have been proposed for balancing the nitrogen flows between neurons and astrocytes in the glutamate/glutamine cycle. All of these cycles depend on the directionality of glutamate dehydrogenase, catalyzing reductive glutamate synthesis (forward reaction) in the neuron in order to capture the ammonia released by phosphate activated glutaminase, while catalyzing oxidative deamination of glutamate (reverse reaction) in the astrocytes to release ammonia for glutamine synthesis. Reanalysis of results from in vivo experiments using 13N and 15N labeled ammonia and leucine in rats suggests that the maximum flux of the alanine/lactate or branched chain amino acid/branched chain amino acid transaminase shuttles between neurons and astrocytes are approximately 3-5 times lower than would be required to account for the ammonia transfer from neurons to astrocytes needed for glutamine synthesis (amide nitrogen) to sustain the glutamate/glutamine cycle. However, in the rat brain both the total ammonia fixation rate by glutamate dehydrogenase and the total branched chain amino acid transaminase activity are sufficient to support a branched chain amino acid/branched chain keto acid shuttle, as proposed by Hutson and coworkers, which would support the de novo synthesis of glutamine in the astrocyte to replace the ∼ 20% of neurotransmitter glutamate that is oxidized. A higher fraction of the nitrogen needs of total glutamate neurotransmitter cycling could be supported by hybrid cycles in which glutamate and tricarboxylic acid cycle intermediates act as a nitrogen shuttle. A limitation of all in vivo studies in animals conducted to date is that none have shown transfer of nitrogen for glutamine amide synthesis, either as free ammonia or via an amino acid from the neurons to the astrocytes. Future work will be needed, perhaps using methods for selectively labeling nitrogen in neurons, to conclusively establish the rate of amino acid nitrogen shuttles in vivo and their coupling to the glutamate/glutamine cycle.
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影响因子：
4.7
作者：
García-Espinosa, María A.;Wallin, Reidar;Sweatt, Andrew J.
通讯作者：
Sweatt, Andrew J.
影响因子：
2.9
作者：
Cole JT;Sweatt AJ;Hutson SM
通讯作者：
Hutson SM
DOI：
10.1073/pnas.0405065101
发表时间：
2004-08-24
影响因子：
11.1
作者：
de Graaf, RA;Mason, GF;Behar, KL
通讯作者：
Behar, KL
影响因子：
6.3
作者：
Cudalbu, Cristina;Lanz, Bernard;Gruetter, Rolf
通讯作者：
Gruetter, Rolf
影响因子：
3.9
作者：
FRENKEL, R
通讯作者：
FRENKEL, R