2-Deoxy-D-Glucose is a glucose analog that has long been known to act as a competitive inhibitor of glucose metabolism. Upon transport into the cells, 2-DG is phosphorylated by hexokinase to 2-DG-P. However, unlike G-6-P, 2-DG-P cannot be further metabolized by phosphohexose isomerase, which converts G-6-P to fructose-6-phosphate . 2-Deoxyglucose-P is trapped and accumulated in the cells, leading to inhibition of glycolysis mainly at the step of phosphorylation of glucose by hexokinase. Inhibition of this rate-limiting step by 2-DG causes a depletion of cellular ATP, leading to blockage of cell cycle progression and cell death in vitro.
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A competitive inhibitor of glucose metabolism.