A Flux Balance of Glucose Metabolism Clarifies the Requirements of the Warburg Effect
A Flux Balance of Glucose Metabolism Clarifies the Requirements of the Warburg Effect
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DOI：
10.1016/j.bpj.2016.07.028
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发表时间：
2016-09-06
影响因子：
3.4
通讯作者：
Locasale, Jason W.
中科院分区：
文献类型：
--
作者：
Dai, Ziwei;Shestov, Alexander A.;Locasale, Jason W.
瓦尔堡效应或有氧糖酵解的特点是在有氧的情况下葡萄糖向乳酸的代谢增加。尽管它在生理学和癌症生物学中广泛流行，但其原因和后果仍不完全清楚。在这里，我们表明，糖酵解中相互作用通量的简单平衡产生了限制，这些限制为糖酵解通量产生乳酸而不是进入线粒体提供了必要的条件。这些条件由细胞氧化还原和能量需求决定。通过分析约束条件并对模型的可行区域进行采样，我们进一步研究了细胞增殖率和线粒体相关的 NADH 氧化和 ATP 产生通量如何相互关联。通过识别瓦尔堡效应实例化所需的通量分布，该分析共同说明了瓦尔堡效应起源的简单性。
The Warburg effect, or aerobic glycolysis, is marked by the increased metabolism of glucose to lactate in the presence of oxygen. Despite its widespread prevalence in physiology and cancer biology, the causes and consequences remain incompletely understood. Here, we show that a simple balance of interacting fluxes in glycolysis creates constraints that impose the necessary conditions for glycolytic flux to generate lactate as opposed to entering into the mitochondria. These conditions are determined by cellular redox and energy demands. By analyzing the constraints and sampling the feasible region of the model, we further study how cell proliferation rate and mitochondria-associated NADH oxidizing and ATP producing fluxes are interlinked. Together this analysis illustrates the simplicity of the origins of the Warburg effect by identifying the flux distributions that are necessary for its instantiation.