Glukoneogenes

Glukoneogenes, also called gluconeogenesis, is a metabolic pathway that synthesizes glucose from non-carbohydrate precursors. In humans, it occurs mainly in the liver and, to a lesser extent, in the kidneys and small intestine, particularly during fasting, starvation, or intense exercise. The pathway functions to maintain blood glucose levels when dietary intake is insufficient.

Gluconeogenesis comprises bypass reactions that reverse three irreversible steps of glycolysis. It begins with pyruvate being converted to oxaloacetate by pyruvate carboxylase in the mitochondria, then to phosphoenolpyruvate by PEP carboxykinase. The later steps bypass the glycolytic sequence from phosphoenolpyruvate down to glucose-6-phosphate, ending with the hydrolysis of glucose-6-phosphate to free glucose by glucose-6-phosphatase. The pathway also uses non-carbohydrate substrates: lactate is converted to pyruvate via the lactate dehydrogenase step, glycerol is converted to glycerol-3-phosphate, and glucogenic amino acids yield intermediates that feed into oxaloacetate or phosphoenolpyruvate.

The net energy cost of gluconeogenesis is substantial, roughly equivalent to several high-energy phosphate bonds per glucose molecule, reflecting its role as a costly way to produce glucose when needed. The pathway is tightly regulated by cellular energy status and hormonal signals. High levels of acetyl-CoA activate pyruvate carboxylase, while citrate inhibits it; AMP inhibits gluconeogenesis, and insulin suppresses the pathway while glucagon and cortisol promote it.

Gluconeogenesis is essential for sustaining brain and red blood cell glucose supply during fasting. It operates in concert with glycolysis and the Cori cycle, balancing metabolic needs during feeding and fasting, and its dysregulation can contribute to metabolic disorders such as hyperglycemia.