gluconeogeen

Gluconeogenesis is a metabolic pathway that generates glucose from non-carbohydrate sources, allowing maintenance of blood glucose during fasting or prolonged exercise. The liver is the primary site of gluconeogenesis, with the kidney contributing during extended fasting or metabolic stress. Substrates include lactate, glycerol, and glucogenic amino acids; in ruminants, other substrates such as propionate can also feed into the pathway.

The pathway largely mirrors glycolysis but uses bypass reactions for its irreversible steps. Pyruvate is converted to oxaloacetate by pyruvate carboxylase in mitochondria, then to phosphoenolpyruvate by PEP carboxykinase in the cytosol. The steps converting 3-phosphoglycerate to glyceraldehyde-3-phosphate and onward to glucose are bypassed by fructose-1,6-bisphosphatase and glucose-6-phosphatase, respectively, allowing glucose to be formed from non-carbohydrate precursors.

Regulation of gluconeogenesis integrates energy status and hormonal signals. Glucagon and cortisol promote gluconeogenesis, partly by increasing transcription of key enzymes such as PEPCK and glucose-6-phosphatase; insulin inhibits the pathway. Allosteric control involves fructose-2,6-bisphosphate, which inhibits fructose-1,6-bisphosphatase. The net result is increased hepatic glucose output to help maintain blood glucose levels during periods of low carbohydrate availability.

Physiological and clinical relevance: gluconeogenesis is essential for glucose homeostasis during fasting and between meals. Dysregulation can contribute to hyperglycemia in diabetes, and the pathway represents a central link between energy balance and carbohydrate metabolism.