It has been known for nearly 100 years that cancer cells use glucose at a much higher rate than do normal cells to generate ATP. This dependence of cancer cells on glycolysis is known as the Warburg effect, which was first described by Otto Warburg in 1925. Recent studies have shown that high levels of lactate production in cancer cells as a result of converting the product of glycolysis, pyruvate, to lactate provides cancer cells with a growth advantage. The enzyme phosphofructokinase-1 (PFK-1) controls flux through glycolysis as a function of allosteric control. Under conditions of high ATP or citrate levels in cells, the catalytic activity of PFK-1 is normally inhibited owing to a high energy charge in the cells. Because cancer cells are highly dependent on glycolysis to provide ATP for cell growth, mutations in PFK-1 that reduce inhibition by ATP and citrate can be advantageous to the cancer cell by maintaining a high rate of metabolic flux through the glycolytic pathway. Two of these mutations, R48C and N426S, have been mapped to the tetrameric PFK-1 protein structure and shown to decrease inhibition of PFK-1 activity by citrate and ATP, respectively.
Everyday BioChem 