Hexokinase 4 (GCK)

Hexokinase 4 (also known as glucokinase or hexokinase D, encoded by the GCK gene) is an enzyme that catalyzes the ATP-dependent phosphorylation of glucose and other hexoses to their 6-phosphate forms, mediating the first committed step in glycolysis[2][1][5]. Uniquely among mammalian hexokinases, hexokinase 4 displays low affinity for glucose and is only active when glucose is abundant, notably within the physiological glucose range encountered in the liver and pancreatic beta cells[1][2][5]. In the pancreas, it acts as a glucose sensor to control insulin secretion; in the liver, it regulates glucose uptake and glycogen synthesis in response to insulin[2]. Mutations in hexokinase 4 are associated with both hyper- and hypoglycemic conditions, most notably MODY2 (a form of monogenic diabetes), and pharmacological modulation of its activity is an emerging strategy for the management of type 2 diabetes[2][5]. Unlike other hexokinases, it is not inhibited by its product, glucose-6-phosphate, allowing it to respond proportionally to increasing glucose concentrations[1][5].

Other names

GlucokinaseHexokinase DGCK

Small molecule activators increase enzymatic affinity for glucose or increase catalytic rate, thereby boosting insulin secretion (pancreatic action) or hepatic glucose uptake and glycogen synthesis (liver action)[2][5].