Gluconeogenesis Overview

Some tissues, such as the brain, red blood cells (RBC), kidney medulla, lens and cornea of the eye, testes, and exercising muscle, require a continuous supply of glucose as a metabolic fuel. Liver glycogen, an essential postprandial source of glucose, can meet these needs for <24 hours in the absence of dietary intake of carbohydrate .

During a prolonged fast, however, hepatic glycogen stores are depleted, and glucose is made from noncarbohydrate precursors. The formation of glucose does not occur by a simple reversal of glycolysis, because the overall equilibrium of glycolysis strongly favors pyruvate formation (that is, the change in standard free energy [ΔG⁰] is negative). Instead, glucose is synthesized de novo by a special pathway, gluconeogenesis, which requires both mitochondrial and cytosolic enzymes. [Note: Deficiencies of gluconeogenic enzymes cause hypoglycemia.] During an overnight fast, ~90% of gluconeogenesis occurs in the liver, with the remaining ~10% occurring in the kidneys. However, during prolonged fasting, the kidneys become major glucoseproducing organs, contributing ~40% of the total glucose production. [Note: The small intestine can also make glucose.] Figure 1 shows the relationship of gluconeogenesis to other essential pathways of energy metabolism.

Figure 1: Gluconeogenesis shown as one of the essential pathways of energy metabolism. The numbered reactions are unique to gluconeogenesis. P = phosphate; CO2 = carbon dioxide.