Glukoneogeneesi

Gluconeogenesis, or glukoneogeneesi, is the metabolic pathway that generates glucose from non-carbohydrate substrates. It is mainly active in the liver and to a lesser extent in the kidneys, especially during fasting or starvation, to maintain blood glucose levels for tissues that rely on glucose, such as the brain and red blood cells.

Substrates for gluconeogenesis include lactate (from anaerobic glycolysis and the Cori cycle), glycerol (from triglyceride breakdown), and glucogenic amino acids such as alanine and glutamine. Some organisms or tissues can also use propionate. The substrates are converted through pathways that ultimately yield glucose-6-phosphate, which can be dephosphorylated to free glucose by glucose-6-phosphatase.

Key bypass steps distinguish gluconeogenesis from glycolysis. Pyruvate is converted to oxaloacetate by pyruvate carboxylase in mitochondria, then oxaloacetate is transported to the cytosol and converted to phosphoenolpyruvate by PEP carboxykinase. The route then proceeds through several steps to form fructose-1,6-bisphosphate, which is hydrolyzed by fructose-1,6-bisphosphatase to fructose-6-phosphate, and finally glucose-6-phosphate is cleaved to glucose by glucose-6-phosphatase in the liver and kidney.

Regulation of gluconeogenesis is tightly controlled by hormones and energy state. Glucagon and epinephrine stimulate the pathway via cAMP signaling, while insulin inhibits it. High acetyl-CoA levels activate pyruvate carboxylase, whereas high energy charge and low NADH/NAD+ ratios dampen the process.

Physiological significance includes maintaining fasting blood glucose, supporting glucose homeostasis during prolonged exercise or starvation, and providing glucose for critical organs. Dysregulation can be associated with metabolic disorders such as hypoglycemia or diabetes.