GKRPmekanismi

GKRPmekanismi refers to the molecular mechanism by which the glucokinase regulatory protein (GKRP) controls the activity and localization of glucokinase (GCK) in liver cells. GKRP, encoded by the GCKR gene, is a cytosolic protein expressed predominantly in the liver and, to a lesser extent, in other tissues. Its primary role is to regulate hepatic glucose utilization by modulating GCK activity and positioning.

The core mechanism involves the dynamic interaction between GKRP and GCK. Under low glucose conditions, GKRP binds GCK and sequesters it in the nucleus, reducing glucokinase activity in the cytosol and slowing glycolysis. When glucose levels rise, GCK is released into the cytosol where it phosphorylates glucose to glucose-6-phosphate, promoting glycolysis and glycogen synthesis. This shift is modulated by metabolite signals: fructose-1-phosphate (F1P) disrupts the GKRP–GCK complex, promoting cytosolic GCK activity, while fructose-6-phosphate (F6P) stabilizes the complex, favoring nuclear retention.

The GKRP mechanism thus acts as a metabolic gatekeeper, linking hepatic glucose sensing to glycolytic flux and glycogen storage. It also influences systemic glucose homeostasis, with implications for conditions such as type 2 diabetes and hepatic steatosis. Pharmacological approaches aim to manipulate this interaction; GKRP inhibitors or glucokinase activators can alter hepatic glucose handling by shifting the balance between nuclear sequestration and cytosolic activity of GCK.

Research on GKRPmekanismi includes structural and functional studies in humans and model organisms, providing insights into the regulatory interface and potential therapeutic targets within hepatic glucose metabolism.