Warburg effect (oncology)

In oncology, the Warburg effect (ˈvɑrbʊərg) is the observation that most cancer cells produce energy predominantly not through the 'usual' citric acid cycle and oxidative phosphorylation in the mitochondria as observed in normal cells, but through a less efficient process of 'aerobic glycolysis' consisting of a high level of glucose uptake and glycolysis followed by lactic acid fermentation taking place in the cytosol, not the mitochondria, even in the presence of abundant oxygen. This observation was first published by Otto Heinrich Warburg, who was awarded the 1931 Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme". The precise mechanism and therapeutic implications of the Warburg effect, however, remain unclear. In fermentation, the last product of glycolysis, pyruvate, is converted into lactate (lactic acid fermentation) or ethanol (alcoholic fermentation). While fermentation produces adenosine triphosphate (ATP) only in low yield compared to the citric acid cycle and oxidative phosphorylation of aerobic respiration, it allows proliferating cells to convert nutrients such as glucose and glutamine more efficiently into biomass by avoiding unnecessary catabolic oxidation of such nutrients into carbon dioxide, preserving carbon-carbon bonds and promoting anabolism. Diagnostically the increased glucose consumption by cancer cells resulting from the Warburg effect is the basis for tumor detection in a Pet scan, in which an injected radioactive glucose analog is detected at higher concentrations in malignant cancers than in other tissues. Around the 1920s, Otto Heinrich Warburg and his group concluded that deprivation of glucose and oxygen in tumor cells leads to a lack of energy, resulting in cell death. Biochemist Herbert Grace Crabtree further extended Warburg's research by discovering environmental or genetic influences. Crabtree observed that yeast, Saccharomyces cerevisiae, prefer fermentation leading to ethanol production over aerobic respiration, in aerobic conditions and in the presence of a high concentration of glucose - the Crabtree effect.