![]() glucose 6-phosphate, dihydroxyacetone phosphate, 3-phosphoglycerate, phosphoenolpyruvate, pyruvate) that participate in the synthesis of these macromolecules. Cell proliferation requires the synthesis of new macromolecules (e.g., nucleic acids, lipids, proteins) and glycolysis provides building blocks (e.g. We have proposed previously that normal proliferating cells and tumor cells need to activate glycolysis despite the presence of oxygen in order to proliferate (10-12). It is also important to note that, although normal proliferating cells and tumor cells activate aerobic glycolysis, these cells also rely on oxphos for their ATP production (4,9).Īlthough it is now accepted that the Warburg effect plays an important role in carcinogenesis and tumor growth, it is not clear why and how this phenomenon occurs. It is important to mention that the metabolic switch from oxphos to aerobic glycolysis is not a unique feature of tumor cells, because it has also been observed in non-transformed proliferating cells (6-8). This phenomenon, called aerobic glycolysis or Warburg effect, has repeatedly been observed and is currently used worldwide as a diagnostic tool to detect malignant tumors (Fluorodeoxyglucose - Positron Emission Tomography: FdG-PET) (5). Several decades later the biochemist Otto Warburg first observed that cancer cells had increased glycolytic activity despite the presence of an adequate oxygen supply (4). This was first noted by Louis Pasteur in the late 19 th century, who observed that the generation of ATP shifted from oxphos to glycolysis when the oxygen levels decreased (Pasteur effect) (1-3). Because oxphos is over ten times more efficient than glycolysis in generating ATP, it is comprehensible that cells generate ATP through oxphos when the oxygen levels are adequate. This transformation consumes NAD +, which can be regenerated by the conversion of pyruvate to lactate. In the glycolytic process, one molecule of glucose is transformed into two molecules of pyruvate resulting in the production of ATP. ![]() Cells can also produce ATP through glycolysis, which takes place in the cytosol and does not require oxygen. Oxphos requires oxygen because the electrons resulting from the oxidation of NADH and FADH 2 need to be ultimately accepted by oxygen. ![]() Most ATP molecules are produced in the mitochondria through oxidative phosphorylation (oxphos), an oxygen-dependent process that couples the oxidation of NADH and FADH 2 with the phosphorylation of ADP to form ATP. IntroductionĬells require energy in the form of adenosine-5-triphosphate (ATP) to carry out numerous cellular processes. We propose that, in the presence of adequate oxygen levels, the intracellular pH may play a key role in determining the way cells obtain energy, an alkaline pH driving aerobic glycolysis and an acidic pH driving oxidative phosphorylation. In this article, we discuss the role of the intracellular pH in the metabolic switch between oxidative phosphorylation and aerobic glycolysis. Understanding the mechanisms involved in the metabolic switch between oxidative phosphorylation and aerobic glycolysis may therefore be important for the development of potential preventive and therapeutic interventions. Recent observations have demonstrated that the activation of aerobic glycolysis plays a major role in carcinogenesis and tumor growth. In fact, normal proliferating cells and tumor cells are known to have a high glycolytic activity in the presence of adequate oxygen levels, a phenomenon known as aerobic glycolysis or the Warburg effect. Although cells must activate glycolysis in the absence of oxygen to produce ATP, it is now accepted that they can activate both glycolysis and oxidative phosphorylation in the presence of oxygen. Since oxidative phosphorylation requires oxygen and generates ATP more efficiently than glycolysis, it has been assumed for many years that the presence or absence of oxygen determines that cells generate energy through oxidative phosphorylation or through glycolysis. Cellular energy in the form of ATP can be produced through oxidative phosphorylation and through glycolysis. ![]()
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