Cancer cells exhibit enhanced lactate production to satisfy biosynthetic adenosine triphosphate requirements and also supply ribose 5‐phosphate (R5P) and nicotinamide adenine dinucleotide phosphate via the pentose phosphate pathway (PPP). Yet, little is known about the mechanism by which glycolytic flux is diverted to PPP to fulfill the increased demand for anabolic precursors and reducing equivalents. Here we show, using a ¹³C‐labeling methodology quantifying glycolysis and the PPP metabolism, that hypoxic cancer cells not only increase net glycolytic flux but also activate the exchange fluxes catalyzed by aldolase and transaldolase. The increased carbon exchange in the upward direction promotes the supplementation of R5P through the nonoxidative PPP and essentially controls the anaplerosis of upper glycolytic metabolites consumed for biosynthesis. This cascade of events is regulated by glyceraldehyde 3‐phosphate dehydrogenase which plays a critical role in diverting metabolites for the synthesis of nucleotide precursors and thus acts as a limiting enzyme under hypoxia. © 2018 American Institute of Chemical Engineers AIChE J, 64: 4289–4296, 2018

中文翻译：

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甘油醛3-磷酸脱氢酶调节非氧化性戊糖磷酸途径，在缺氧肿瘤细胞中提供合成代谢前体

癌细胞具有增强的乳酸生成能力，可以满足生物合成三磷酸腺苷的需求，还可以通过戊糖磷酸途径（PPP）提供5-磷酸核糖（R5P）和烟酰胺腺嘌呤二核苷酸磷酸。然而，关于将糖酵解通量转移到PPP来满足对合成代谢前体的增加需求和减少当量的机制的了解甚少。我们在这里展示，使用¹³C标记法可量化糖酵解和PPP代谢，即低氧癌细胞不仅增加净糖酵解通量，而且还激活醛缩酶和反醛缩酶催化的交换通量。向上碳交换的增加通过非氧化PPP促进了R5P的补充，并从根本上控制了生物合成所消耗的上层糖酵解代谢物的异常状态。这种级联反应受3-磷酸甘油醛脱氢酶的调节，该酶在转移代谢产物以合成核苷酸前体中起关键作用，因此在缺氧条件下起限制性酶的作用。©2018美国化学工程师学会AIChE J，64：4289-4296，2018