In vivo nuclear magnetic resonance studies of glutamate-γ-aminobutyric acid-glutamine cycling in rodent and human cortex:: the central role of glutamine

In vivo nuclear magnetic resonance studies of glutamate-γ-aminobutyric acid-glutamine cycling in rodent and human cortex:: the central role of glutamine
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DOI:
10.1093/jn/131.9.2498s
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发表时间:
2001-09-01
影响因子:
4.2
通讯作者:
Rothman, DL
Rothman, DL
中科院分区:
医学2区
文献类型:
--
作者:
Behar, KL;Rothman, DL

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多年来人们已经认识到,大脑谷氨酸和γ-氨基丁酸(GABA)(主要的兴奋性和抑制性神经递质)的代谢与涉及谷氨酰胺的神经元和星形胶质细胞之间的底物循环有关。然而,这些通量在体内的定量意义尚不清楚。最近的啮齿动物体内 C-13 和 N-15 NMR 以及人体 C-13 NMR 研究表明,谷氨酰胺合成量很大,并且补充神经递质谷氨酸和 GABA 所必需的总谷氨酸-GABA-谷氨酰胺循环通量占净谷氨酰胺合成的 80% 以上。在啮齿动物皮层的研究中,在大范围的皮层电活动中,葡萄糖氧化速率与总谷氨酸-GABA-谷氨酰胺循环通量之间存在线性关系。这些通量之间发现的摩尔化学计量关系(类似于 1:1)表明它们具有共同的机制,并且谷氨酸-GABA-谷氨酰胺循环与皮质葡萄糖利用的主要部分耦合。因此,谷氨酰胺似乎在大脑皮层的正常功能能量学中发挥着核心作用。
It has been recognized for many years that the metabolism of brain glutamate and gamma -aminobutyric acid (GABA), the major excitatory and inhibitory neurotransmitters, Is linked to a substrate cycle between neurons and astrocytes involving glutamine. However, the quantitative significance of these fluxes in vivo was not known. Recent in vivo C-13 and N-15 NMR studies in rodents and C-13 NMR in humans indicate that glutamine synthesis is substantial and that the total glutamate-GABA-glutamine cycling flux, necessary to replenish neurotransmitter glutamate and GABA, accounts for > 80% of net glutamine synthesis. In studies of the rodent cortex, a linear relationship exists between the rate of glucose oxidation and total glutamate-GABA-glutamine cycling flux over a large range of cortical electrical activity. The molar stoichiometric relationship (similar to1:1) found between these fluxes suggests that they share a common mechanism and that the glutamate-GABA-glutamine cycle is coupled to a major fraction of cortical glucose utilization. Thus, glutamine appears to play a central role in the normal functional energetics of the cerebral cortex.