Quantitative importance of the pentose phosphate pathway determined by incorporation of 13C from [2-13C]- and [3-13C]glucose into TCA cycle intermediates and neurotransmitter amino acids in functionally intact neurons
Quantitative importance of the pentose phosphate pathway determined by incorporation of 13C from [2-13C]- and [3-13C]glucose into TCA cycle intermediates and neurotransmitter amino acids in functionally intact neurons
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DOI：
10.1038/jcbfm.2012.85
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发表时间：
2012-09-01
影响因子：
6.3
通讯作者：
Sonnewald, Ursula
中科院分区：
文献类型：
--
作者：
Brekke, Eva M. F.;Walls, Anne B.;Sonnewald, Ursula
大脑对氧化损伤高度敏感，磷酸戊糖途径(PPP)已被证明受到阿尔茨海默病和创伤性脑损伤等病理条件的影响。虽然这一途径已经在完整的大脑和星形胶质细胞中进行了研究，但对神经元中的PPP知之甚少。用[2-C-13]葡萄糖或[3-C-13]葡萄糖孵育培养的大脑皮层和小脑神经元，定量检测PPP的活性。在两种类型的神经元中，PPP的活性都比糖酵解低好几倍。虽然C-13标记的葡萄糖通过PPP的代谢似乎并不有助于产生可释放的乳酸，但它有助于标记三羧酸(TCA)循环中间体和相关氨基酸。根据谷氨酸等位体计算，PPP活性占皮质神经元葡萄糖代谢的6%，占小脑神经元葡萄糖代谢的4%。这是首次证明葡萄糖通过PPP生成的丙酮酸有助于在TCA循环中合成用于氧化的乙酰辅酶A。此外，葡萄糖的C-13标记被结合到谷氨酸中的事实证明，PPP的氧化和非氧化阶段在神经元中都是活跃的。《脑血流与代谢杂志》(2012年)32期，1788年-1799年；doi：10.1038/jcbfm.2012.85；2012年6月20日在线出版
The brain is highly susceptible to oxidative injury, and the pentose phosphate pathway (PPP) has been shown to be affected by pathological conditions, such as Alzheimer's disease and traumatic brain injury. While this pathway has been investigated in the intact brain and in astrocytes, little is known about the PPP in neurons. The activity of the PPP was quantified in cultured cerebral cortical and cerebellar neurons after incubation in the presence of [2-C-13] glucose or [3-C-13] glucose. The activity of the PPP was several fold lower than glycolysis in both types of neurons. While metabolism of C-13-labeled glucose via the PPP does not appear to contribute to the production of releasable lactate, it contributes to labeling of tricarboxylic acid (TCA) cycle intermediates and related amino acids. Based on glutamate isotopomers, it was calculated that PPP activity accounts for similar to 6% of glucose metabolism in cortical neurons and similar to 4% in cerebellar neurons. This is the first demonstration that pyruvate generated from glucose via the PPP contributes to the synthesis of acetyl CoA for oxidation in the TCA cycle. Moreover, the fact that C-13 labeling from glucose is incorporated into glutamate proves that both the oxidative and the nonoxidative stages of the PPP are active in neurons. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1788-1799; doi:10.1038/jcbfm.2012.85; published online 20 June 2012