Medical knowledge

Glucose Metabolism and Lactate Production in Cancer Cells👇

📎Glucose Uptake and Phosphorylation:
Glucose enters cells via glucose transporters (GLUT) through facilitated diffusion. Once inside, it’s phosphorylated by hexokinase (HK) to form glucose-6-phosphate, consuming one ATP molecule and trapping glucose within the cell.

📎Pathways for Glucose-6-Phosphate:
Glucose-6-phosphate can either enter the pentose phosphate pathway (PPP) or glycolysis. In glycolysis, it is further converted into fructose 1,6-bisphosphate by phosphofructokinase (PFK), consuming another ATP. Both hexokinase and phosphofructokinase are key regulatory enzymes in this process.

📎Glycolysis and ATP Production:
Fructose 1,6-bisphosphate is split into two 3-carbon molecules, which then undergo phosphorylation and oxidation to form pyruvate. This process generates two ATP and two NADH molecules per glucose molecule.

📎NADH in Mitochondria and Cancer Cells:
In cells with functional mitochondria, NADH fuels the electron transport chain. However, cancer cells limit their NADH pool as it can inhibit PFK and slow glycolysis. Instead, they use NADH to convert pyruvate into lactate via lactate dehydrogenase (LDH).

📎Lactate Export and Tumor Microenvironment:
Excess lactate is transported out of the cell into the tumor microenvironment (TME) by monocarboxylate transporters (MCT). In the TME, lactate can accumulate and lower the pH to between 6 and 7, creating an acidic environment.

💡Credit: Barba, I.; Carrillo-Bosch, L.; Seoane, J. Targeting the Warburg Effect in Cancer: Where Do We Stand? Int. J. Mol. Sci. 2024, 25, 3142.