Zwingmann C, Brand A, Richter-Landsberg C, Leibfritz D
Department of Chemistry, University of Bremen, Bremen, Germany.
Dev Neurosci. 1998;20(4-5):417-26. doi: 10.1159/000017339.
Glutamine synthesis, the major pathway of ammonia detoxification, and the intracellular concentration of organic osmolytes in primary astrocytes and F98 glioma cells were investigated with multinuclear magnetic resonance spectroscopy. Acute exposure to ammonia (3 h incubation with NH4Cl) raised the concentration of glutamine and other amino acids, such as glutamate and aspartate, and decreased myo-inositol, hypotaurine, and taurine concentrations. The loss of these osmolytes was partially reversed by co-treatment with the glutamine synthetase inhibitor, methionine sulphoximine. Glutamate, the precursor of glutamine, is provided by stimulated anaplerotic flux via pyruvate carboxylase and glutamate dehydrogenase activity. Thus, the glutamine increase and myo-inositol decrease observed by in vivo magnetic resonance spectroscopy on patients with hepatic encephalopathy may be due to the disturbed osmoregulation in astrocytes caused by accumulation of glutamine and the subsequent loss of organic osmolytes.
利用多核磁共振波谱研究了谷氨酰胺合成（氨解毒的主要途径）以及原代星形胶质细胞和F98胶质瘤细胞中有机渗透溶质的细胞内浓度。急性暴露于氨（与NH4Cl孵育3小时）会提高谷氨酰胺和其他氨基酸（如谷氨酸和天冬氨酸）的浓度，并降低肌醇、亚牛磺酸和牛磺酸的浓度。谷氨酰胺合成酶抑制剂甲硫氨酸亚砜亚胺共同处理可部分逆转这些渗透溶质的损失。谷氨酰胺的前体谷氨酸是通过丙酮酸羧化酶和谷氨酸脱氢酶活性刺激的回补通量提供的。因此，在肝性脑病患者体内磁共振波谱观察到的谷氨酰胺增加和肌醇减少可能是由于谷氨酰胺积累导致星形胶质细胞渗透压调节紊乱以及随后有机渗透溶质的损失所致。
