How is glycolysis regulated in response to cellular energy status?

Glycolysis is regulated at three key steps catalyzed by irreversible enzymes. Hexokinase is inhibited by its product glucose-6-phosphate (product inhibition). Phosphofructokinase-1 (PFK-1), the main regulatory enzyme, is allosterically inhibited by ATP and citrate (signals of high energy), and activated by AMP, ADP, and fructose-2,6-bisphosphate (signals of low energy or high glucose). Pyruvate kinase is activated by fructose-1,6-bisphosphate (feedforward activation) and inhibited by ATP and alanine. Hormonal regulation (insulin promotes, glucagon inhibits glycolysis) works through changes in enzyme amounts and fructose-2,6-bisphosphate levels, coordinating with gluconeogenesis regulation.