Why does hexokinase have a low km

Glucosephosphate and ADP are the products of this reaction. Hexokinase undergoes an induced-fit conformational change when it binds to glucose, which ultimately prevents the hydrolysis of ATP. It also experiences potent allosteric inhibition under physiological concentrations by its immediate products, glucosephosphate [4].

This is a mechanism by which the influx of substrate into the glycolytic pathway is controlled. Hexokinase activates glycoloysis by phosphorylating glucose. Since the phosphorylation of glucose to glucosephosphate is the rate limiting step of glucose metabolism, hexokinase has a very important role in regulating healthy glucose levels in the human body [7]. Hexokinase has high affinity, thus a low Km, for glucose. Tissues where hexokinase is present use glucose at low blood serum levels.

G6P inhibits hexokinase by binding to the N-terminal domain this is simple feedback inhibition. It competitively inhibits the binding of ATP [8]. If the cell is not using the G6P that it is making, then it stops making it.

In this way, hexokinase can also slow down glycolysis. Hexokinase I is thought to be the "pacemaker" of glycolysis in brain tissue and red blood cells [4]. Inorganic phosphate allosterically relieves hexokinase of inhibition by G6P [8].

Hexokinase 3D structures. For additional information, see: Carbohydrate Metabolism. Mechanism of liver glucokinase. Mol Cell Biochem. Glucokinase vs. Other Hexokinases: Glucokinase is unique from other hexokinase in kinetic properties and is coded by a different gene. The difference of glucokinase from the other hexokinases is that glucokinase has a lower affinity, thus a higher Km, for glucose.

The reduced affinity for glucose allows the activity of glucokinase to differ under physiological conditions according to the amount of glucose present. Essentially, this means that it operates only when serum glucose levels are high.

Other tissues need to use glucose at lower serum levels and thus use the higher affinity lower Km hexokinase. Glucosephosphate inhibits hexokinase and, if the cell is not using up the G6P that it is making, then it should stop making it, thus making the process a product inhibition. In contrast, G6P does not inhibit glucokinase, and this allows it to remain active in storing as much glucose as possible in the presence of high glucose levels.

Glucokinase Structure: Glucokinase also contains and conformation. Glucokinase consists of one chain or subunit of amino acids forming a monomeric molecule consisting of 13 alpha helices and 5 beta sheets that can phosporylate glucose and other hexoses. The chain is folded into two distinct regions, a small and large domain. Glucokinase has one active binding site for glucose and one for ATP, which is the energy source for phosphorylation.

This active binding site is located between the small and large domains. The carboxyl terminus is part of the alpha 13 helix, which codes for the region that forms half of the binding site for glucose.

Glucokinase can be modulated to form an inactive and active complex. The inactive conformation forms when the alpha 13 helix has been modulated away from the rest of the molecule forming a large space.

This space is too large to bind glucose so it is said to be in the inactive form. The alternative is when the alpha 13 helix is modulated to form a smaller space thus activating the protein [4].

Glucokinase includes the where glucose forms hydrogen bonds at the bottom of the deep crevice between the large domain and the small domain.

E, E shown in green of the large domain, T, K shown in red of the small domain, and N, D shown in yellow of a connecting region form hydrogen bonds with glucose. The shows a different conformation. The again shows structural differences. The differences in these two conformations allows glucokinase to function properly in different levels of glucose concentration.

Proposed Mechanism for Glucokinase: As described above, glucokinase has a distinct conformation change from the active and inactive form. Experiments have also shown an intermediate open form based on analysis of the movement between the active and inactive form. The switch in conformations between the active form and the intermediate is a kinetically faster step than the change between the intermediate and the inactive form.

The inactive form of gluckokinase is the thermodynamically favored unless there is glucose present. Glucokinase does not change conformation until the glucose molecule binds. The conformation change may be triggered by the interaction between Asp and the glucose molecule. Hexokinases play an important role in glucose metabolism, as glucose is the most important substrate of hexokinases. Hexokinases are found in many organisms including bacteria, plants and mammals.

On the other hand, increased hexokinase activity is detected in various human tumors and is associated with metastasis.

Kinetic curves showing Hexokinase activity in positive control included in kit , lysates from HeLa 0. Publishing research using ab? Please let us know so that we can cite the reference in this datasheet. There are currently no Customer reviews or Questions for ab