Figure 3
From: Activated lymphocytes as a metabolic model for carcinogenesis
Glycolytic isozyme switching promotes high rates of glycolysis. Activated T cells, cancer cells and other highly proliferative cells express different glycolytic isozymes in comparison to quiescent cells, increasing glycolytic flux. One key step in glycolysis is the phosphorylation of fructose 6-phosphate by phosphofructokinase-1 (PFK-1). PFK-1 is allosterically activated by fructose 2,6-bisphosphate and allosterically inhibited by ATP. Both activated T cells and tumor cells express isoform 3 of the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB). In contrast, naïve T cells express PFKFB isoform 2. PFKFB3 differs from PFKFB2 in that it has low phosphatase activity, leading to the accumulation of fructose 2,6-bisphosphate and localized depletion of ATP. This results in increased PFK-1 activity and higher rates of glycolysis.