Glucose transport and glycolysis pathway

Glucose transport and glycolysis represent the fundamental metabolic processes by which cells take up glucose and convert it into energy and biosynthetic precursors. In healthy tissues, glucose is typically oxidized via the tricarboxylic acid cycle and oxidative phosphorylation; however, many diseased cells, particularly in cancer, exhibit the Warburg effect, characterized by a dramatic increase in glucose uptake and aerobic glycolysis. This metabolic reprogramming supports the high energy demands and rapid biomass production required for cell proliferation and survival. Therapeutic targeting of this pathway involves the use of small molecules to inhibit glucose transporters (e.g., GLUT1) or key regulatory enzymes such as Hexokinase 2, Phosphofructokinase, and Pyruvate Kinase M2. By disrupting these steps, drugs aim to selectively starve glucose-addicted cells, leading to growth arrest or apoptosis. Beyond oncology, targeting glucose metabolism is also explored in treating infections like malaria and managing metabolic disorders. However, the central role of glucose in normal physiology, particularly in the brain and red blood cells, presents significant challenges for achieving therapeutic selectivity and avoiding systemic toxicity.

Other names

Warburg effectAerobic glycolysisGlucose metabolismGlycolytic pathwayGlucose uptake and catabolism

Inhibition of glucose uptake via GLUT transporters and suppression of glycolytic flux through the inhibition of rate-limiting enzymes such as Hexokinase 2 and Pyruvate Kinase M2.