Glucose-6-phosphatase catalytic subunit alpha (G6PC1)

Glucose-6-phosphatase catalytic subunit alpha (G6PC1) is a key enzyme located in the endoplasmic reticulum membrane of the liver, kidney, and intestinal cells. It catalyzes the terminal step of both glycogenolysis and gluconeogenesis by hydrolyzing glucose-6-phosphate into free glucose and inorganic phosphate, allowing glucose to be released into the bloodstream to maintain systemic homeostasis [UniProt P35575, PubMed 29485006]. Genetic deficiency of this enzyme results in Glycogen Storage Disease Type Ia (Von Gierke disease), a severe metabolic disorder characterized by life-threatening hypoglycemia, hepatomegaly, and lactic acidosis [NIH StatPearls, PubMed 31536299]. Conversely, in Type 2 Diabetes, the enzyme's activity is often pathologically elevated, contributing to excessive hepatic glucose production and fasting hyperglycemia [PubMed 15102554]. While G6PC1 is a theoretical target for small-molecule inhibitors to treat diabetes, the primary therapeutic challenge remains balancing glycemic control with the risk of inducing GSD-like symptoms such as hepatic steatosis and lactic acidosis [PubMed 11502471].

Other names

Glucose-6-phosphataseG6PaseG6PCG6Pase-alphaGlucose-6-phosphatase catalytic subunit 1

Inhibition of the catalytic subunit to reduce hepatic glucose output or replacement therapy/gene therapy to restore activity in deficiency states.