Figure 3

Glycolytic pathways in tumor cells. Sketch of the most important glucose-degrading metabolic pathways in a tumor cell. Glucose uptake into the cytoplasm is accomplished via specific transpcorters (GLUTs) that are often overexpressed in tumor cells. Here the enzyme hexokinase (HK) phosphorylates glucose to glucose-6-phosphate (glucose-6-P). This metabolite either gets degraded to pyruvate via several intermediate steps of glycolysis or serves as the precursor for conversion into ribulose-5-phosphate in the oxidative part of the pentose phosphate pathway (PPP). In the PPP, CO₂ gets released and the reducing equivalent NADPH is produced. The generated ribulose-5-phosphate either serves as the basis for de novo synthesis of nucleotides or is converted to various C3–C7 sugars through the transketolase/transaldolase reaction in the non-oxidative part of the PPP. Pyruvate, the end product of glycolysis, usually gets transported into the mitochondria, converted to acetyl-CoA and channeled into the TCA cycle for oxidative degradation. In case of insufficient oxygenation, dysfunctional mitochondria or metabolic reprogramming through hyperactivation of AKT–mTOR signaling, pyruvate is increasingly converted to lactate via the enzyme lactate dehydrogenase (LDH). Lactate gets transported out of the cell by monocarboxylate transporters (MCTs). The PI3K–AKT pathways increases glycolytic rate by the mechanisms depicted and described in the main text. Dashed arrows indicate several intermediate steps.