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通过代谢通量分析揭示完整原代神经元中戊糖磷酸途径被低估。

Underestimation of the pentose-phosphate pathway in intact primary neurons as revealed by metabolic flux analysis.

机构信息

Institute of Functional Biology and Genomics (IBFG), University of Salamanca-CSIC, Salamanca, Spain.

出版信息

J Cereb Blood Flow Metab. 2013 Dec;33(12):1843-5. doi: 10.1038/jcbfm.2013.168. Epub 2013 Sep 25.

DOI:10.1038/jcbfm.2013.168
PMID:24064491
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3851909/
Abstract

The rates of glucose oxidized at glycolysis and pentose-phosphate pathway (PPP) in neurons are controversial. Using [3-(3)H]-, [1-(14)C]-, and [6-(14)C]glucose to estimate fluxes through these pathways in resting, intact rat cortical primary neurons, we found that the rate of glucose oxidized through PPP was, apparently, ∼14% of total glucose metabolized. However, inhibition of PPP rate-limiting step, glucose-6-phosphate (G6P) dehydrogenase, increased approximately twofold the glycolytic rate; and, knockdown of phosphoglucose isomerase increased ∼1.8-fold the PPP rate. Thus, in neurons, a considerable fraction of fructose-6-phosphate returning from the PPP contributes to the G6P pool that re-enters PPP, largely underestimating its flux.

摘要

神经元糖酵解和磷酸戊糖途径(PPP)中葡萄糖氧化的速率存在争议。使用[3-(3)H] - 、[1-(14)C] - 和[6-(14)C] - 葡萄糖来估计在休息、完整的大鼠皮质原代神经元中这些途径的通量,我们发现 PPP 途径中葡萄糖氧化的速率显然约为总葡萄糖代谢的 14%。然而,抑制 PPP 限速步骤葡萄糖-6-磷酸(G6P)脱氢酶使糖酵解速率增加约两倍;磷酸葡萄糖异构酶的敲低使 PPP 速率增加了约 1.8 倍。因此,在神经元中,从 PPP 返回的相当一部分果糖-6-磷酸有助于重新进入 PPP 的 G6P 池,这大大低估了其通量。

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