Glucosio6fosfatasi

Glucosio6fosfatasi, known in English as glucose-6-phosphatase, is a microsomal enzyme that catalyzes the hydrolysis of glucose-6-phosphate to glucose and inorganic phosphate. It plays a central role in maintaining blood glucose during fasting by enabling hepatic glucose production through gluconeogenesis and glycogenolysis. The enzyme is predominantly expressed in the liver and kidney.

Biochemical mechanism and complex: The catalytic activity resides in the glucose-6-phosphatase catalytic subunit (G6PC). Functionally, it requires the glucose-6-phosphate transporter (G6PT, encoded by SLC37A4) to move glucose-6-phosphate from the cytosol into the endoplasmic reticulum lumen where hydrolysis occurs. A paralog, G6PC3, exists in humans and has distinct physiological roles.

Genetics and disease: Mutations in G6PC cause glycogen storage disease type I, also known as von Gierke disease. This condition presents with severe fasting hypoglycemia, hepatomegaly, lactic acidosis, hyperuricemia, and hyperlipidemia due to impaired hepatic glucose production. Defects in the G6PC–G6PT system disrupt normal glucose release during fasting.

Regulation and physiology: Glucose-6-phosphatase activity is integrated into hormonal control of metabolism. Glucagon and epinephrine raise cyclic AMP and promote hepatic glucose output, while insulin signaling tends to suppress glucose production. The enzyme thus contributes to maintaining euglycemia between meals and during prolonged fasting.

Clinical notes: Management of glycogen storage disease type I focuses on maintaining normoglycemia through frequent feeding and cornstarch therapy, along with monitoring for metabolic and hepatic complications. Understanding the G6PC–G6PT system is essential for appreciating hepatic glucose production and related metabolic diseases.