What is gluconeogenesis and when does it occur?

Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors (pyruvate, lactate, glycerol, amino acids) primarily in the liver and kidney cortex. It occurs during fasting or prolonged exercise when blood glucose levels drop. The pathway largely reverses glycolysis but uses different enzymes at three irreversible steps: pyruvate carboxylase and PEPCK bypass pyruvate kinase; fructose-1,6-bisphosphatase bypasses PFK-1; and glucose-6-phosphatase bypasses hexokinase. Gluconeogenesis consumes 6 ATP equivalents per glucose formed. The Cori cycle recycles lactate from muscle to liver for gluconeogenesis, maintaining glucose homeostasis.