Glucose-6-phosphatase catalytic subunit (G6PC) (G6PC)

Glucose-6-phosphatase (G6Pase) is a multi-protein complex located in the endoplasmic reticulum (ER) membrane, primarily expressed in the liver, kidney, and small intestine. It serves as the gatekeeper for endogenous glucose production by catalyzing the hydrolysis of glucose-6-phosphate into free glucose and inorganic phosphate, the final step in both gluconeogenesis and glycogenolysis (UniProt P35575). The complex consists of a catalytic subunit (G6PC) and a translocase (G6PT) that transports the substrate into the ER lumen. In patients with Type 2 Diabetes, G6Pase activity is often upregulated, contributing to excessive hepatic glucose production and fasting hyperglycemia (PubMed 11511235). Conversely, loss-of-function mutations in the G6PC gene result in Glycogen Storage Disease Type Ia (von Gierke disease), a condition marked by severe fasting hypoglycemia, lactic acidosis, and hepatomegaly (StatPearls NBK448176). While G6Pase inhibitors have been investigated as potential anti-diabetic agents, their clinical development is challenged by the risk of inducing hypoglycemia and hepatic steatosis.

Other names

G6PaseG6PC1Glucose-6-phosphatase alphaGSD1a proteinHepatic glucose-6-phosphataseGlucose-6-phosphatase catalytic subunit 1

Inhibition of the glucose-6-phosphatase enzyme complex to reduce hepatic glucose output by blocking the final step of gluconeogenesis and glycogenolysis.