Glucose synthesis from precursors, key regulatory steps, and substrate cycling
Gluconeogenesis synthesizes glucose from non-carbohydrate precursors (lactate, amino acids, glycerol) primarily in the liver during fasting. It reverses 7 of 10 glycolytic steps but must bypass three irreversible reactions with unique enzymes: pyruvate carboxylase + PEPCK (bypass pyruvate kinase), fructose-1,6-bisphosphatase (bypass PFK-1), and glucose-6-phosphatase (bypass hexokinase). The pathway costs 6 ATP equivalents per glucose and is reciprocally regulated with glycolysis via glucagon/insulin signaling through PFK-2/FBPase-2 and their effects on fructose-2,6-bisphosphate levels.