Gluconeogenese

Gluconeogenesis, sometimes written gluconeogenese in some languages, is a metabolic pathway that synthesizes glucose from non-carbohydrate precursors. It occurs mainly in the liver, with a significant contribution from the renal cortex during prolonged fasting, and to a lesser extent in the small intestine. The process helps maintain blood glucose levels when dietary carbohydrate intake is low or energy demand is high.

Primary substrates include lactate (the Cori cycle), glycerol released from adipose tissue, and glucogenic amino acids such as alanine and glutamine; some pathways can also use propionate in certain organisms. The pathway comprises four main bypass reactions that reverse irreversible steps of glycolysis: pyruvate is converted to phosphoenolpyruvate via pyruvate carboxylase (mitochondria) and PEP carboxykinase; fructose-1,6-bisphosphatase bypasses the phosphofructokinase-1 step; and glucose-6-phosphatase converts glucose-6-phosphate to free glucose.

Energy and reducing equivalents are required for gluconeogenesis. Net consumption per molecule of glucose formed is typically 4 ATP and 2 GTP, plus reducing equivalents supplied through NADH via shuttle systems. The liver and kidney coordinate these reactions with cytosolic and mitochondrial enzymes and shuttle mechanisms that transfer intermediates between compartments.

Regulation is tightly controlled. Insulin inhibits gluconeogenesis, while glucagon and cortisol stimulate it through cAMP-dependent signaling and transcriptional changes. Fructose-2,6-bisphosphate acts as a potent allosteric regulator, inhibiting fructose-1,6-bisphosphatase and thereby linking glycolysis and gluconeogenesis.

Defects in key enzymes, such as glucose-6-phosphatase, cause disorders like Von Gierke disease, characterized by hypoglycemia and impaired glucose release.