PKM2, a Central Point of Regulation in Cancer Metabolism

Figure 1

Schematic illustrating the cancer utilization of the metabolic pathways. Pyruvate kinase catalyzes the last step of glycolysis by converting PEP and ADP to pyruvate and ATP, respectively. PKM2 dimers and tetramers possess low and high levels of Pyruvate kinase activity, respectively. With reduced enzymatic activity, PKM2 dimer drives aerobic glycolysis, which allows the intermediate metabolites to be used for the synthesis of nucleotides, amino acids, and lipids and the production of reduced NADPH (see the pentose phosphate pathway). HIF-1 upregulates the indicated proteins. GLUT: glucose transporter, HK: hexokinase, G6PD: glucose-6-phosphate dehydrogenase, HIF-1: hypoxia-inducible factor 1, LDHA: lactate dehydrogenase A, PDK1: pyruvate dehydrogenase kinase isoenzyme 1, and PDH: pyruvate dehydrogenase.