Haber S, Lapidot A
Department of Organic Chemistry, Weizmann Institute of Science, 76 100, Rehovot, Israel.
Brain Res. 2001 Mar 30;896(1-2):102-17. doi: 10.1016/s0006-8993(01)02065-0.
The principle substrate for brain metabolism is glucose, which provides both energy and the carbon skeletons of glutamate and glutamine, via the TCA cycle. The existence of two distinct cerebral metabolic compartments, neurons and glia, involved in glutamate and glutamine synthesis, respectively, is a widely accepted concept. In previous work, the relative glucose flux via pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC) in adult rabbit brain, using 13C NMR isotopomer analysis of glutamate and glutamine, was quantified. In this work, manifestation of cerebral compartmentation in the near-term fetal rabbit was investigated, using the above approach. Following infusion of [U-13C]glucose into maternal circulation (1 mg/kg per min) for 60-70 min, fetal brains were excised and brain extracts were studied by 13C NMR. The labelling patterns of fetal cerebral metabolites differed from those observed in the young adult brain. The most significant differences were found for glutamine labelling patterns. We suggested that these differences are a result of increased utilization of non-labeled fuels, mainly beta-hydroxybutyrate (beta-HBA) in the glia, the site of glutamine synthesis. In addition, we have shown that acute exposure to elevated beta-HBA levels leads to increased uptake, but not utilization, into the fetal rabbit brain; no increase in uptake is observed in the adult brain. We have also demonstrated that during short-term starvation, although no changes are detected in plasma and cerebral glucose levels in the fetal and young adult brain, amino acid levels and energy metabolism are altered in the young adult brain.
大脑代谢的主要底物是葡萄糖，它通过三羧酸循环为大脑提供能量以及谷氨酸和谷氨酰胺的碳骨架。存在两个不同的脑代谢区室，即神经元和神经胶质细胞，它们分别参与谷氨酸和谷氨酰胺的合成，这是一个被广泛接受的概念。在之前的研究中，通过对谷氨酸和谷氨酰胺进行¹³C NMR 同位素异构体分析，定量测定了成年兔脑中经由丙酮酸脱氢酶（PDH）和丙酮酸羧化酶（PC）的相对葡萄糖通量。在本研究中，采用上述方法对近足月胎儿兔脑区室化的表现进行了研究。向母体循环中输注[U-¹³C]葡萄糖（每分钟 1 mg/kg）持续 60 - 70 分钟后，取出胎儿脑并通过¹³C NMR 研究脑提取物。胎儿脑代谢物的标记模式与成年幼兔脑不同。在谷氨酰胺标记模式中发现了最显著的差异。我们认为这些差异是由于未标记燃料（主要是神经胶质细胞中谷氨酰胺合成部位的β-羟基丁酸酯（β-HBA））利用增加所致。此外，我们已经表明，急性暴露于升高的β-HBA 水平会导致胎儿兔脑摄取增加，但不会导致利用增加；成年脑中未观察到摄取增加。我们还证明，在短期饥饿期间，尽管在胎儿和成年幼兔脑中未检测到血浆和脑葡萄糖水平的变化，但成年幼兔脑中氨基酸水平和能量代谢发生了改变。
