Glyukokinaasi

Glyukokinaasi, also known as glucokinase (GCK), is a cytosolic enzyme that catalyzes the ATP-dependent phosphorylation of glucose to glucose-6-phosphate, the first step in glycolysis and a key control point in glucose metabolism. It has a relatively high Km for glucose, meaning it acts when blood glucose is elevated, and it is not inhibited by glucose-6-phosphate, unlike other hexokinases.

Glyukokinaasi is predominantly expressed in the liver and pancreatic beta cells, with roles in both liver glucose disposal and insulin secretion. In the pancreas, it functions as part of the glucose sensing mechanism that links extracellular glucose levels to insulin release. In the liver, it promotes glycolysis and glycogen synthesis, contributing to postprandial glucose clearance and energy storage.

Regulation of glucokinase involves its interaction with the glucokinase regulatory protein (GKRP) in the liver. GKRP can sequester glucokinase in the nucleus at low glucose concentrations, reducing activity, while higher glucose levels promote release into the cytosol and increased catalytic activity. The enzyme’s kinetic properties and regulatory mechanisms position it as a central regulator of hepatic glucose handling and systemic glucose homeostasis.

Clinical significance includes genetic variations in the GCK gene. Inactivating mutations cause maturity-onset diabetes of the young type 2 (MODY2); homozygous mutations can result in permanent neonatal diabetes. Common GCK variants influence fasting glucose and diabetes susceptibility. Therapeutically, glucokinase activators are explored to enhance hepatic glucose utilization, though they carry risks such as hypoglycemia and lipid effects.