Glucokinase

Glucokinase is an enzyme that traps glucose in the liver. Glucokinase is part of the hexokinase enzyme family and is sometimes referred to as hexokinase IV. This enzyme functions by attaching phosphorus to glucose inside the liver and forming glucose-6-phosphate (G-6-P). Glucokinase differs from the other hexokinases, which are found in muscle and other organs. Specifically, glucokinase is highly effective at converting glucose into G-6-P in the liver, while muscle hexokinase can only convert a limited amount of glucose into G-6-P. In muscle, elevated levels of G-6-P inhibit hexokinase activity (referred to as negative feedback). While in the liver, elevated levels of G-6-P do not inhibit glucokinase activity. Through the actions of glucokinase, the liver plays a more critical role in the storage of excess glucose than does the muscle. Once glucokinase has trapped glucose in the liver, the liver will decide which metabolic pathway for glucose to enter. This is one reason why the liver is referred to as the gatekeeper of metabolism.

G-6-P is the enzyme that opposes glucokinase. G-6-P works by removing the attached phosphorus (from glucokinase) and creating free glucose. This permits the stored glucose in the liver to be released into the plasma. Glucokinase is regulated by other by-products of glucose metabolism such as fructose-1-phosphate (activates) and fructose-6-phosphate (inhibits). Glucokinase regulatory protein (GKRP) also affects the enzymatic functioning of glucokinase enzyme. GKRP will inhibit glucokinase when glucose levels are low in the blood and activate it when glucose levels are high in the blood, subsequently allowing for either the release or removal of glucose in the body.

Glucokinase is also present in the β-cells of the pancreas. The β-cells are responsible for producing and releasing insulin, the hormone that regulates blood sugar levels. Glucokinase is present in the β-cells in order to sense the presence of glucose, then signal the production of insulin, and release insulin into the body. Glucokinase is regulated by insulin only on a long-term basis such that chronically high levels of insulin may alter glucokinase expression.

Maturity onset of diabetes in youth (MODY) is a rare, genetic form of diabetes mellitus. Patients who suffer from MODY are primarily children who are hyperglycemic (high blood sugar) but have normal β-cell function. Several genetic mutations have been found to be responsible for MODY including a mutation in the gene that makes glucokinase. In this genetic disorder, there is decreased glucokinase level.