FIGURE 12-4 Allosteric regulation of glucose metabolism. The key regulatory enzyme in glycolysis, phosphofructokinase-1, is allosterically activated by AMP and fructose 2,6-bisphosphate, which are elevated when the cell’s energy stores are low. The enzyme is inhibited by ATP and citrate, both of which are elevated when the cell is actively oxidizing glucose to CO₂ (i.e., when energy stores are high). Later we will see that citrate is generated during stage II of glucose oxidation. Phosphofructokinase-2 is a bifunctional enzyme: its kinase activity forms fructose 2,6-bisphosphate from fructose 6-phosphate, and its phosphatase activity catalyzes the reverse reaction. Insulin, which is released by the pancreas when blood glucose levels are high, promotes phosphofructokinase-2 kinase activity and thus stimulates glycolysis. At low blood glucose, glucagon is released by the pancreas and promotes phosphofructokinase-2 phosphatase activity in the liver, indirectly slowing down glycolysis.