Cerebral glutamine metabolism under hyperammonemia determined in vivo by localized 1H and 15N NMR spectroscopy
Cerebral glutamine metabolism under hyperammonemia determined in vivo by localized 1H and 15N NMR spectroscopy
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DOI：
10.1038/jcbfm.2011.173
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发表时间：
2012-04-01
影响因子：
6.3
通讯作者：
Gruetter, Rolf
中科院分区：
文献类型：
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作者：
Cudalbu, Cristina;Lanz, Bernard;Gruetter, Rolf
脑谷氨酰胺合成酶（GS）是谷氨酸-谷氨酰胺循环的组成部分，发生在神经胶质区室。体内磁共振波谱（MRS）允许无创测量代谢物的浓度和合成速率。N-15 MRS是C-13 MRS的替代方法。将来自氨的标记N-15掺入脑谷氨酰胺中可以测量与氮代谢相关的几种代谢反应，包括谷氨酸-谷氨酰胺循环。为了测量N-15掺入谷氨酰胺的位置5 N和谷氨酸和谷氨酰胺的位置2N，我们开发了一种新的N-15脉冲序列，以首次在大鼠脑中体内同时检测[5-N-15] Gln和[2-N-15]Gln + Glu。此外，我们还在同一实验中首次测量了局部H-1光谱，用于直接测量净谷氨酰胺积累。H-1和N-15 MRS数据的数学建模允许减少假设的数量并提供GS的可靠测定（0.30 +/- 0.050 μ mol/g/min），表观神经传递（0.26 +/- 0.030 μ mol/g/min），谷氨酸脱氢酶（0.029 +/- 0.002 μ mol/g/min）和净谷氨酰胺积累（0.033 +/- 0.001 μ mol/g/min）。这些结果表明，GS和净谷氨酰胺积累下高氨血症的增加，支持其含义在脑氨解毒的概念。Journal of Cerebral Blood Flow & Metabolism（2012）32，696-708; doi：10.1038/jcbfm.2011.173; 2011年12月14日在线发表
Brain glutamine synthetase (GS) is an integral part of the glutamate-glutamine cycle and occurs in the glial compartment. In vivo Magnetic Resonance Spectroscopy (MRS) allows noninvasive measurements of the concentrations and synthesis rates of metabolites. N-15 MRS is an alternative approach to C-13 MRS. Incorporation of labeled N-15 from ammonia in cerebral glutamine allows to measure several metabolic reactions related to nitrogen metabolism, including the glutamate-glutamine cycle. To measure N-15 incorporation into the position 5N of glutamine and position 2N of glutamate and glutamine, we developed a novel N-15 pulse sequence to simultaneously detect, for the first time, [5-N-15] Gln and [2-N-15]Gln + Glu in vivo in the rat brain. In addition, we also measured for the first time in the same experiment localized H-1 spectra for a direct measurement of the net glutamine accumulation. Mathematical modeling of H-1 and N-15 MRS data allowed to reduce the number of assumptions and provided reliable determination of GS (0.30 +/- 0.050 mu mol/g per minute), apparent neurotransmission (0.26 +/- 0.030 mu mol/g per minute), glutamate dehydrogenase (0.029 +/- 0.002 mu mol/g per minute), and net glutamine accumulation (0.033 +/- 0.001 mu mol/g per minute). These results showed an increase of GS and net glutamine accumulation under hyperammonemia, supporting the concept of their implication in cerebral ammonia detoxification. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 696-708; doi:10.1038/jcbfm.2011.173; published online 14 December 2011