glucokinases

Glucokinases are a group of enzymes that catalyze the phosphorylation of glucose. This reaction is the first step in glucose metabolism, where glucose is converted into glucose-6-phosphate. This process is crucial for both energy production and storage within cells. In mammals, the most well-known glucokinase is glucokinase (GCK), also known as hexokinase IV.

Glucokinase plays a vital role in regulating blood glucose levels. It is primarily found in the liver and pancreatic beta cells. In the liver, glucokinase acts as a glucose sensor, stimulating glucose uptake and glycogen synthesis when blood glucose levels are high. This helps to lower blood sugar after a meal. In pancreatic beta cells, glucokinase is also a key regulator of insulin secretion. When glucose enters beta cells, glucokinase phosphorylates it, leading to an increase in ATP production. This ATP rise triggers the closure of ATP-sensitive potassium channels, causing membrane depolarization and calcium influx, ultimately stimulating insulin release.

Mutations in the GCK gene can lead to genetic disorders. Loss-of-function mutations are a common cause of maturity-onset diabetes of the young (MODY) type 2, characterized by mild, stable hyperglycemia. Gain-of-function mutations, though rarer, can result in hyperinsulinism-hyperglycemia syndrome, where excessive insulin is secreted, leading to severe hypoglycemia. The kinetic properties of glucokinase, particularly its high Km (low affinity for glucose) compared to other hexokinases, allow it to function effectively as a sensor in the physiological range of blood glucose concentrations.