University Medicine Berlin (Charité), Institute of Biochemistry, Berlin, Germany.
FEBS J. 2011 Jul;278(14):2436-59. doi: 10.1111/j.1742-4658.2011.08174.x. Epub 2011 Jun 10.
Many tumor types exhibit an impaired Pasteur effect, i.e. despite the presence of oxygen, glucose is consumed at an extraordinarily high rate compared with the tissue from which they originate - the so-called 'Warburg effect'. Glucose has to serve as the source for a diverse array of cellular functions, including energy production, synthesis of nucleotides and lipids, membrane synthesis and generation of redox equivalents for antioxidative defense. Tumor cells acquire specific enzyme-regulatory mechanisms to direct the main flux of glucose carbons to those pathways most urgently required under challenging external conditions such as varying substrate availability, presence of anti-cancer drugs or different phases of the cell cycle. In this review we summarize the currently available information on tumor-specific expression, activity and kinetic properties of enzymes involved in the main pathways of glucose metabolism with due regard to the explanation of the regulatory basis and physiological significance of the Warburg effect. We conclude that, besides the expression level of the metabolic enzymes involved in the glucose metabolism of tumor cells, the unique tumor-specific pattern of isozymes and accompanying changes in the metabolic regulation below the translation level enable tumor cells to drain selfishly the blood glucose pool that non-transformed cells use as sparingly as possible.
许多肿瘤类型表现出一种受损的巴斯德效应，即尽管存在氧气，葡萄糖的消耗速度仍比其起源组织（所谓的“沃伯格效应”）高得惊人。葡萄糖必须作为多种细胞功能的来源，包括能量产生、核苷酸和脂质的合成、膜合成以及抗氧化防御的氧化还原当量的产生。肿瘤细胞获得了特定的酶调节机制，以将葡萄糖碳的主要通量引导到最急需的途径，这些途径在外部条件具有挑战性时尤为重要，例如底物可用性的变化、抗癌药物的存在或细胞周期的不同阶段。在这篇综述中，我们总结了目前关于参与葡萄糖代谢主要途径的酶的肿瘤特异性表达、活性和动力学特性的信息，同时考虑了沃伯格效应的调节基础和生理意义的解释。我们的结论是，除了参与肿瘤细胞葡萄糖代谢的代谢酶的表达水平外，同工酶的独特肿瘤特异性模式以及翻译水平以下代谢调节的伴随变化，使肿瘤细胞能够自私地耗尽非转化细胞尽可能节约使用的血糖池。
