Glucokinase is a hexokinase enzyme which facilitates the phosphorylation of glucose to glucose-6-phosphate (G6P). Alternate names for this enzyme are human hexokinase IV and ATP:D-hexose 6-phosphotransferase, EC 18.104.22.168. The common name, glucokinase, is derived from its minimal reactivity with mannose and fructose, unlike hexokinases I, II, and III. Molecular weight is about 50 kD.
The phosphorylation reaction mediated by glucokinase is:
Phosphorylation of glucose to G6P is the first step of glycolysis, but the higher KM of glucokinase for glucose compared to other hexokinases leaves them more important initiators of glycolysis for most cells.
Glucokinase is primarily located in liver cells and pancreatic islet cells, where it serves a more specialized function as a glucose sensor . The activity of glucokinase is minimal below a threshold intracellular glucose level of 5 mmol/l (about 90 mg/dl). It is also less inhibited by the product, G6P, so it continues to work in the presence of high glucose levels. In these cells, most of the G6P is consumed anaerobically in the citric acid cycle of the mitochondria, producing far more ATP than is consumed by the initial phosphorylation.
Glucokinase regulates insulin secretion
In islet beta cells, glucokinase activity is serves as a principal control for the secretion of insulin in response to rising levels of blood glucose. As G6P is consumed in the mitochondria, increasing amounts of ATP initiate a series of processes that result in release of insulin.
Mutations causing hypoglycemia or diabetes
Mutations of the glucokinase gene can change the efficiency of glucose binding and phosphorylation, increasing or decreasing the sensitivity of beta cell insulin secretion in response to glucose. Specific mutations have been discovered that can result in excessive insulin secretion (causing a form of hyperinsulinemic hypoglycemia) or deficient insulin secretion (causing a form of diabetes referred to as MODY.