Mason G F, Rothman D L, Behar K L, Shulman R G
Department of Molecular Biophysics, Yale University School of Medicine, New Haven, Connecticut.
J Cereb Blood Flow Metab. 1992 May;12(3):434-47. doi: 10.1038/jcbfm.1992.61.
A mathematical model of cerebral glucose metabolism was developed to analyze the isotopic labeling of carbon atoms C4 and C3 of glutamate following an intravenous infusion of [1-13C]glucose. The model consists of a series of coupled metabolic pools representing glucose, glycolytic intermediates, tricarboxylic acid (TCA) cycle intermediates, glutamate, aspartate, and glutamine. Based on the rate of 13C isotopic labeling of glutamate C4 measured in a previous study, the TCA cycle rate in rat brain was determined to be 1.58 +/- 0.41 mumol min-1 g-1 (mean +/- SD, n = 5). Analysis of the difference between the rates of isotopic enrichment of glutamate C4 and C3 permitted the rate of exchange between alpha-ketoglutarate (alpha-KG) and glutamate to be assessed in vivo. In rat brain, the exchange rate between alpha-KG and glutamate is between 89 +/- 35 and 126 +/- 22 times faster than the TCA cycle rate (mean +/- SD, n = 4). The sensitivity of the calculated value of the TCA cycle rate to other metabolic fluxes and to concentrations of glycolytic and TCA cycle intermediates was tested and found to be small.
建立了一个脑葡萄糖代谢的数学模型，用于分析静脉注射[1-13C]葡萄糖后谷氨酸碳原子C4和C3的同位素标记情况。该模型由一系列相互耦合的代谢池组成，分别代表葡萄糖、糖酵解中间产物、三羧酸（TCA）循环中间产物、谷氨酸、天冬氨酸和谷氨酰胺。根据先前研究中测得的谷氨酸C4的13C同位素标记率，确定大鼠脑内TCA循环速率为1.58±0.41 μmol·min-1·g-1（平均值±标准差，n = 5）。分析谷氨酸C4和C3同位素富集率之间的差异，能够在体内评估α-酮戊二酸（α-KG）与谷氨酸之间的交换速率。在大鼠脑中，α-KG与谷氨酸之间的交换速率比TCA循环速率快89±35至126±22倍（平均值±标准差，n = 4）。测试了TCA循环速率计算值对其他代谢通量以及糖酵解和TCA循环中间产物浓度的敏感性，发现其敏感性较小。
