Figure 1.

Glucose metabolism in cancer cells. In strategy 1, glucose is uptake is by GLUT1, which is a glucose transporter overexpressed in cancer cells, and follows the glycolytic pathway to pyruvate. The first step is the phosphorylation by hexokinase (HK) and the main isoform upregulated in cancer is HK₂. Under anaerobiosis, pyruvate is converted to lactate, with the regeneration of NAD⁺ that feeds glycolysis. This way is a source of energy for cancer cells and supplies intermediates like ribose-5-phosphate and NADPH that are required for cell proliferation. In strategy 2, pyruvate obtained by glycolysis is transformed in Acetyl-Coenzyme-A (Acetyl-CoA) that enters in the mitochondrial Krebs cycle and follows oxidative phosphorylation (OXPHOS), the main source of ATP in a normal cell. Finally, in strategy 3, the cancer cell may turn in mitochondrial uncoupling, because it could use substrates that are different of glucose as a carbon source like fatty acids, aspartate, and glutamine that feeds the Krebs cycle (anaplerotic reactions). There is a mitochondrial carrier named uncoupling protein 2 (UCP2), that has been connected with proliferation and anaplerotic mitochondrial metabolism in cancer cells. The proliferating cells can choose more than one strategy at a time.