ABSTRACT

Gluconeogenesis synthesizes glucose from noncarbohydrate precursors and is important for the maintenance of blood glucose levels during starvation or during vigorous exercise. Gluconeogenesis occurs mainly in the liver and to a lesser extent in the kidney. Most enzymes of gluconeogenesis are cytosolic, but pyruvate carboxylase and glucose 6-phosphatase are located in the mitochondrial matrix and bound to the smooth endoplasmic reticulum, respectively. In glycolysis, glucose is metabolized to pyruvate. In gluconeogenesis, pyruvate is metabolized to glucose. Thus, in principle, gluconeogenesis appears to be a reversal of glycolysis. Glycerol can act as a substrate for glucose synthesis by conversion to dihydroxyacetone phosphate, an intermediate in gluconeogenesis. Glycolysis generates two adenosine triphosphate (ATP) net per glucose whereas gluconeogenesis uses four ATPs and two guanosine triphosphate (GTP) per glucose. Glycolysis and gluconeogenesis are made responsive to starvation by the level of the regulatory molecule fructose 2,6-bisphosphate (F-2,6-BP).