Glucokinase (Hexokinase-4) (GCK)

Glucokinase (GK), also known as hexokinase-4, is a monomeric enzyme that serves as the primary glucose sensor in the human body, predominantly expressed in the liver and pancreatic beta-cells (1.3.1, 1.4.1). Unlike other hexokinases, GK has a low affinity for glucose and a sigmoidal kinetic response, allowing it to respond to physiological changes in blood glucose levels (1.3.1, 1.4.4). In the pancreas, it triggers insulin secretion in response to rising glucose, while in the liver, it promotes glucose uptake and glycogen synthesis (1.3.4, 1.4.1). Due to its central role in glucose homeostasis, GK is a major therapeutic target for Type 2 Diabetes Mellitus (T2DM) (1.4.1, 1.4.3). Small-molecule glucokinase activators (GKAs) aim to enhance its activity to lower blood sugar; however, challenges such as hypoglycemia and lipid metabolism disturbances have complicated drug development (1.1.1, 1.2.1). Mutations in the GCK gene are linked to various metabolic disorders, including Maturity-Onset Diabetes of the Young type 2 (MODY2) and congenital hyperinsulinism (1.1.2, 1.3.2).

Other names

Hexokinase-4Hexokinase IVHK IVHK4GCKMODY2FGQTL3GLKHHF3HXKPLGLK

Allosteric activation of glucokinase to increase its affinity for glucose and its catalytic rate, thereby enhancing glucose-stimulated insulin secretion in the pancreas and increasing hepatic glucose uptake and glycogen synthesis (1.4.1, 1.5.3).