Determination of the rate of the glutamate glutamine cycle in the human brain by in vivo 13C NMR
Determination of the rate of the glutamate glutamine cycle in the human brain by in vivo 13C NMR
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DOI：
10.1073/pnas.96.14.8235
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发表时间：
1999-07-06
影响因子：
11.1
通讯作者：
Rothman, DL
中科院分区：
文献类型：
--
作者：
Shen, J;Petersen, KF;Rothman, DL
最近在大鼠模型中进行的 C-13 NMR 研究表明，谷氨酸/谷氨酰胺循环在大脑皮层中高度活跃，并以大约 1:1 的化学计量与增量葡萄糖氧化耦合。为了确定人类皮质中是否存在高水平的谷氨酸能活性，测定了静息时的人类枕叶/顶叶中的三羧酸循环、谷氨酰胺合成和谷氨酸/谷氨酰胺循环的速率。在输注[1-C-13]-葡萄糖期间，获得了标记掺入[4-C-13]-谷氨酸和[4-C-13]-谷氨酰胺的时间过程的体内C-13 NMR谱。使用我们在大鼠中验证的代谢模型，我们计算出总三羧酸循环率为 0.77 +/- 0.07 mu mol/min/g（平均值 +/- SD，n = 6），葡萄糖氧化率为 0.39 +/- 0.04 mu mol/min/g，谷氨酸/谷氨酰胺循环率为 0.32 +/- 0.05 pmol/min/g（平均值 +/- SD，n = 6）。 6).与大鼠大脑皮层的研究一致，谷氨酸/谷氨酰胺循环是人脑静息时的主要代谢通量，其速率约为葡萄糖氧化的 80%。
Recent C-13 NMR studies in rat models have shown that the glutamate/glutamine cycle is highly active in the cerebral cortex and is coupled to incremental glucose oxidation in an approximate to 1:1 stoichiometry. To determine whether a high level of glutamatergic activity is present in human cortex, the rates of the tricarboxylic acid cycle, glutamine synthesis, and the glutamate/glutamine cycle were determined in the human occipital/parietal lobe at rest. During an infusion of [1-C-13]-glucose, in vivo C-13 NMR spectra were obtained of the time courses of label incorporation into [4-C-13]-glutamate and [4-C-13]-glutamine. Using a metabolic model we have validated in the rat, we calculated a total tricarboxylic acid cycle rate of 0.77 +/- 0.07 mu mol/min/g (mean +/- SD, n = 6), a glucose oxidation rate of 0.39 +/- 0.04 mu mol/min/g, and a glutamate/glutamine cycle rate of 0.32 +/- 0.05 pmol/min/g (mean +/- SD, n = 6). In agreement with studies in rat cerebral cortex, the glutamate/glutamine cycle is a major metabolic flux in the resting human brain with a rate approximate to 80% of glucose oxidation.