Catabolic efficiency of aerobic glycolysis: the Warburg effect revisited.
Catabolic efficiency of aerobic glycolysis: the Warburg effect revisited.
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DOI：
10.1186/1752-0509-4-58
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发表时间：
2010-05-06
影响因子：
--
通讯作者：
Oltvai ZN
中科院分区：
文献类型：
--
作者：
Vazquez A;Liu J;Zhou Y;Oltvai ZN
即使在氧气存在的情况下，癌细胞也会同时表现出糖酵解和乳酸分泌以及线粒体呼吸，这一现象被称为华宝效应。维持这种混合代谢表型似乎是违反直觉的，因为有氧糖酵解在每摩尔葡萄糖的ATP产量方面远不如线粒体呼吸有效。在这里，我们通过扩展代谢效率的概念来解决这一明显的矛盾。我们研究了一个ATP生产的约化通量平衡模型，该模型受葡萄糖摄取能力和细胞质溶剂容量的限制，后者量化了可以占据细胞内空间的最大大分子数量。在较低的葡萄糖摄取率下，我们发现线粒体呼吸确实是产生ATP的最有效途径。然而，在葡萄糖摄取阈值以上，有氧糖酵解的逐渐激活和线粒体呼吸的轻微下降会导致最高的ATP产生速率。我们的分析表明，对于所有具有高葡萄糖摄取能力的快速增殖的哺乳动物细胞来说，Warburg效应是一种有利的分解代谢状态。这是因为，虽然有氧糖酵解在每葡萄糖摄取的ATP产量方面不如线粒体呼吸有效，但在所需的溶剂容量方面却更有效。这些结果可能与试图针对癌症新陈代谢的化疗策略有直接关系。
Cancer cells simultaneously exhibit glycolysis with lactate secretion and mitochondrial respiration even in the presence of oxygen, a phenomenon known as the Warburg effect. The maintenance of this mixed metabolic phenotype is seemingly counterintuitive given that aerobic glycolysis is far less efficient in terms of ATP yield per moles of glucose than mitochondrial respiration. Here, we resolve this apparent contradiction by expanding the notion of metabolic efficiency. We study a reduced flux balance model of ATP production that is constrained by the glucose uptake capacity and by the solvent capacity of the cell's cytoplasm, the latter quantifying the maximum amount of macromolecules that can occupy the intracellular space. At low glucose uptake rates we find that mitochondrial respiration is indeed the most efficient pathway for ATP generation. Above a threshold glucose uptake rate, however, a gradual activation of aerobic glycolysis and slight decrease of mitochondrial respiration results in the highest rate of ATP production. Our analyses indicate that the Warburg effect is a favorable catabolic state for all rapidly proliferating mammalian cells with high glucose uptake capacity. It arises because while aerobic glycolysis is less efficient than mitochondrial respiration in terms of ATP yield per glucose uptake, it is more efficient in terms of the required solvent capacity. These results may have direct relevance to chemotherapeutic strategies attempting to target cancer metabolism.
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影响因子：
8.8
作者：
Michelakis, E. D.;Webster, L.;Mackey, J. R.
通讯作者：
Mackey, J. R.
影响因子：
--
作者：
Lin, Chen-Sung;Wang, Liang-Shun;Wei, Yau-Huei
通讯作者：
Wei, Yau-Huei
影响因子：
2.8
作者：
Gambhir, A;Korke, R;Hu, WS
通讯作者：
Hu, WS
DOI：
10.1385/1-59259-284-8:107
发表时间：
2002-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Nomoto, Shuji;Sanchez-Cespedes, Montserrant;Sidransky, David
通讯作者：
Sidransky, David
影响因子：
37.3
作者：
de Groof AJ;te Lindert MM;van Dommelen MM;Wu M;Willemse M;Smift AL;Winer M;Oerlemans F;Pluk H;Fransen JA;Wieringa B
通讯作者：
Wieringa B