Glycolysis: High aerobic glycolysis

During anaerobic conditions, glycolysis is the cellular mechanism to obtain ATP, by fermentation. However, in mammalian cells, glycolysis is coupled with aerobic respiration. In the presence of oxygen, mitochondria take up pyruvate, the end-product of glycolysis, and further oxidize it into CO2 and water. As a result, the flux through the glycolytic pathway is lower during aerobic conditions since the full oxidation of one molecule of pyruvate (equivalent to one-half molecule of glucose) can lead to 18 times more ATP. Malignant rapidly-growing tumor cells, however, have glycolytic rates that are up to 200 times higher than that of their normal tissues of origin, despite the ample availability of oxygen. A classical explanation holds that the local depletion of oxygen within the tumor is the cause of the high glycolytic rate in tumor cells. Nevertheless, there is also strong experimental evidence that attributes these high aerobic glycolytic rates to an overexpressed form of mitochondrially-bound hexokinase responsible for driving the high glycolytic activity when oxygen is not necessarily depleted. This phenomenon was first described in 1930 by Otto Warburg, and hence it is referred to as the Warburg Effect. This has a current important medical application, as aerobic glycolysis by malignant tumors is utilized clinically to diagnose and monitor treatment responses of cancers by imaging uptake of 2-18F-2-deoxyglucose (a radioactive modified hexokinase substrate) with positron emission tomography (PET)


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