Glukose6phosphatase

Glucose-6-phosphatase, sometimes written as Glukose-6-phosphatase, is an endoplasmic reticulum–resident, membrane-bound enzyme that catalyzes the hydrolysis of glucose-6-phosphate to glucose and inorganic phosphate. It is a key component of endogenous glucose production, enabling the final steps of gluconeogenesis and glycogenolysis in liver, kidney, and, to a lesser extent, intestine, particularly during fasting.

The glucose-6-phosphate hydrolysis system comprises several catalytic subunits and a translocator. The catalytic subunits in humans include G6PC1, G6PC2, and G6PC3, which differ in tissue distribution: G6PC1 is mainly expressed in liver and kidney; G6PC2 is enriched in pancreatic islets; G6PC3 is widely expressed. The transport of glucose-6-phosphate into the ER lumen is mediated by the glucose-6-phosphate transporter (G6PT, encoded by SLC37A4). In the lumen of the ER, G6Pase hydrolyzes G6P to glucose and phosphate, and the products are transported back to the cytosol or released into the bloodstream as appropriate.

Genetic defects of G6PC cause glycogen storage disease type I (von Gierke disease), a disorder of impaired glucose production characterized by severe fasting hypoglycemia, lactic acidosis, hyperuricemia, hepatomegaly, and hyperlipidemia. Management focuses on maintaining euglycemia, often through regular feeding and uncooked cornstarch. Mutations in G6PC3 give rise to a congenital neutropenia syndrome and may be associated with developmental anomalies. Variants in G6PC2 can influence fasting glucose levels and, in some populations, diabetes risk, reflecting its role in islet glucose homeostasis.