glucosa6fosfatasa

Glucose-6-phosphatase (G6Pase) is a microsomal enzyme that catalyzes the hydrolysis of glucose-6-phosphate to glucose and inorganic phosphate. This reaction represents the final step in both gluconeogenesis and glycogenolysis, enabling the liver and kidney to release glucose into the bloodstream during fasting.

The activity of G6Pase is carried out by a multi-subunit complex. The catalytic subunit is encoded by the G6PC gene. Glucose-6-phosphate is transported into the endoplasmic reticulum lumen by the transporter protein SLC37A4 (G6PT), where the G6Pase reaction takes place. The G6PC–G6PT complex functions together to complete the final dephosphorylation step.

Expression of G6Pase is highest in the liver and kidney, with additional expression in the small intestine. Related isoforms, such as G6PC2 in pancreatic beta cells and G6PC3 in many tissues, have distinct roles. The enzyme complex localizes to endoplasmic reticulum membranes, placing the hydrolysis reaction in a compartment that links cytosolic glucose production to cellular handling and secretion.

Regulation of G6Pase activity is tied to metabolic state and hormonal signals. During fasting, hormones such as glucagon promote gluconeogenic and glycogenolytic flux, increasing the need for glucose release and upregulating G6Pase activity. Insulin generally opposes these fasting responses. Genetic defects can disrupt glucose homeostasis.

Clinical significance: Mutations in G6PC or SLC37A4 cause glycogen storage disease type I (von Gierke disease), characterized by severe fasting hypoglycemia, lactic acidosis, hyperuricemia, hepatomegaly, and hyperlipidemia. Management focuses on maintaining euglycemia with frequent meals and cornstarch supplementation; in some cases, liver transplantation may be considered.