gluconeogenic

Gluconeogenic is an adjective related to gluconeogenesis, the metabolic pathway by which glucose is synthesized from non-carbohydrate precursors. In mammals, gluconeogenesis occurs mainly in the liver and to a lesser extent in the kidneys, with the small intestine contributing under certain conditions. This pathway helps maintain blood glucose during fasting or increased energy demand when dietary carbohydrate is scarce.

Substrates used for gluconeogenesis include lactate, glycerol, and glucogenic amino acids such as alanine, glutamine, serine, and glycine. Lactate produced by anaerobic glycolysis is transported to the liver and converted to pyruvate, while glycerol released from adipose tissue is transformed into dihydroxyacetone phosphate and other intermediates. Amino acids are deaminated and converted into intermediates that feed into the pathway.

Key steps in gluconeogenesis involve bypassing irreversible glycolytic reactions. Pyruvate is first carboxylated to oxaloacetate in mitochondria by pyruvate carboxylase, then converted to phosphoenolpyruvate by PEP carboxykinase. Subsequent reactions regenerate glucose-6-phosphate, which is finally dephosphorylated by glucose-6-phosphatase to yield free glucose. Glucose-6-phosphatase is located in the endoplasmic reticulum of liver and kidney cells, enabling glucose export into the bloodstream.

Regulation of gluconeogenesis is tightly controlled by hormonal and energy-status signals. Glucagon and cortisol promote gluconeogenic gene expression and flux via cAMP-mediated signaling, while insulin inhibits it. Cellular energy status, including levels of ATP, NADH, and the regulator fructose-2,6-bisphosphate, also modulates the balance between gluconeogenesis and glycolysis.

Physiologically, gluconeogenesis maintains euglycemia during fasting and prolonged exercise. Dysregulation can contribute to hyperglycemia in metabolic disorders such as diabetes.