Glucokinase

Glucokinase is an enzyme that facilitates the phosphorylation of glucose to glucose-6-phosphate (G6P), an essential step in glucose metabolism. This process occurs in the liver and pancreatic beta cells, playing a critical role in maintaining blood sugar levels within a normal range. Glucokinase acts as a glucose sensor, regulating the rate of glucose entry into the glycolytic pathway and its subsequent storage as glycogen, primarily in the liver, or its use for energy production.

Unlike other hexokinases, glucokinase has a high Km (Michaelis constant) for glucose, meaning it is most active when glucose concentrations are high, such as after a meal. This property allows it to serve as a regulatory enzyme for glucose metabolism, ensuring that glucose is only phosphorylated and stored when it is abundant.

In the pancreas, glucokinase's activity affects the release of insulin, a hormone that lowers blood glucose levels by increasing cellular uptake of glucose and its conversion to glycogen. Mutations in the gene encoding glucokinase can lead to disorders of glucose metabolism, such as maturity onset diabetes of the young (MODY), specifically MODY2, and persistent hyperinsulinemic hypoglycemia of infancy (PHHI).

The regulation of glucokinase activity involves a complex interplay between its concentration, the availability of glucose, and the presence of regulatory proteins such as glucokinase regulatory protein (GKRP). GKRP binds to glucokinase in the absence of glucose, sequestering it in the nucleus and preventing its action. When glucose levels rise, glucokinase is released from GKRP and translocates to the cytoplasm where it can exert its enzymatic function.