Gluconeogenesis

Gluconeogenesis is the metabolic pathway that produces glucose from noncarbohydrate precursors. It is particularly important when glucose is not being supplied continuously from food, such as during fasting. In humans, gluconeogenesis occurs mainly in the liver and also in the kidneys, with the renal contribution becoming more important during prolonged fasting .^1,2

Major gluconeogenic precursors include lactate, glycerol, and glucogenic amino acids such as alanine. These compounds enter the pathway at different points. Lactate and alanine can be converted to pyruvate, while glycerol enters through an intermediate called dihydroxyacetone phosphate. The pathway ultimately produces glucose that can be released into the circulation to help maintain blood glucose .^1,2

Gluconeogenesis shares several reversible reactions with glycolysis but is not simply glycolysis running backward. Three strongly favorable steps of glycolysis cannot be directly reversed under normal cellular conditions. Gluconeogenesis bypasses these steps using different enzymes, including pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase. The pathway requires energy, including ATP and GTP .^1,2

Gluconeogenesis is also distinct from glycogenolysis. Glycogenolysis releases glucose units from previously stored glycogen, whereas gluconeogenesis synthesizes glucose from smaller metabolic precursors. During fasting, both processes can contribute to glucose production. Insulin generally suppresses hepatic gluconeogenesis, while glucagon promotes hepatic gluconeogenesis and glycogenolysis .^1,2