The Warburg Effect refers to the phenomenon that occurs in most cancer cells where instead of generating energy with a low rate of glycolysis followed by oxidizing pyruvate via the Krebs cycle in the mitochondria, the pyruvate from a high rate of glycolysis undergoes lactic acid fermentation in the cytosol. As the Krebs cycle is an aerobic process, in normal cells lactate production is reserved for anaerobic conditions. However, cancer cells preferentially utilize glucose for lactate production via this “aerobic glycolysis”, even when oxygen is plentiful. The Warburg Effect is thought to be the result of mutations to oncogenes and tumour suppressor genes. It may be an adaptation to low-oxygen environments within tumours, the result of cancer genes shutting down the mitochondria, or a mechanism to aid cell proliferation via increased glycolysis. Proliferation may occur due to the accumulation of glycolytic intermediates (which lead to the production of nucleotides, amino acids, and fatty acids) after the final enzymatic reaction of glycolysis (phosphoenolpyruvate into pyruvate) is slowed down. This reaction produces lactic acid which leads to a low pH microenvironment and the lactate shuttle can activate angiogenesis factors from surrounding cells. The Warburg Effect involves numerous pathways, including growth factor stimulation, transcriptional activation, and glycolysis promotion.

Aerobic Glycolysis (Warburg Effect) References