Figure 1.

Comparison of glucose metabolism in a normal and cancer cell and potential inhibitors of glucose metabolism l. The majority of normal cells utilize glucose as a substrate in the glycolytic pathway. Then pyruvate, a product in this process, enters the mitochondria and after being converted into acetylo-CoA enters the tricarboxylic acid cycle. In cancer cells, overexpression of GLUT transporters causes increased glucose uptake compared to normal cells. Increased expression of glycolytic enzymes is also observed. M2 isoform of pyruvate kinase shows reduced catalytic activity which allows the directing of part of the created G-6-P to the pentose phosphate pathway. The PKM2 isoform also stimulates HIF-1 into increased transcriptional activity by binding to the transactivation domain of HIF1-α subunit. The activation of HIF results in increased expression of the key elements of glucose metabolism, for example, GLUT transporters, enzymes of the glycolytic pathway, and lactate dehydrogenase. Most of the pyruvate created in cancer cells is converted into lactate by lactate dehydrogenase. Lactate is transported outside of cells by the monocarboxylate transporters, whose amount is elevated in cancer cells.