Hexokinase (ADP-Dependent)

Related Reading

Introductions

Hexokinase (HK) is a transferase, not very specific, inhibited by glucose-6-phosphate and ADP, with a small Km (Mie constant) and high affinity to act against a wide range of six-carbon sugars.

Classification

There are four different types of hexokinase known to be controlled by different genes on different chromosomes; in humans, for example, hexokinase I is controlled by a gene on chromosome 10, hexokinase II is controlled by a gene on chromosome 2, hexokinase III is controlled by a gene on chromosome 5, and hexokinase IV is controlled by a gene on chromosome 7 (also known as glucokinase). (Note In recent years, researchers have used genomic approaches to characterize hexokinase genes in various vertebrate species and close relatives and have found a similar HK gene, named hexokinase structural domain protein 1 (HKDC1), which is thought to be the fifth hexokinase.

Chemical composition

• In biochemistry, kinases are a class of enzymes that transfer phosphate groups from a high-energy donor molecule to a specific target molecule (substrate); this process is called phosphorylation.
• In general, the purpose of phosphorylation is to "activate" or "energize" the substrate molecule, increasing its energy so that it can participate in subsequent reactions with negative changes in free energy. All kinases require the presence of a divalent metal ion (e.g. Mg²⁺ or Mn²⁺), which acts as a stabilizer of the high-energy bonds of the donor molecule and provides the possibility for phosphorylation to occur.
• The largest kinase group is protein kinases. Protein kinases act on specific proteins and alter their activity. These kinases play a wide range of roles in cell signaling and its complex life activities.

Reaction process

Hexokinase can catalyze the phosphorylation reaction from ATP at the hexose 6 position. The reaction process is

Hexose ATP-hexose-6-phosphate ADP

The affinity for α-D glucose is high (Km=1×10-5M), and phosphorylation of other hexoses is also possible. The equilibrium of this reaction is shifted to the right. ΔG°'=4.0 kcal. The enzyme is widely present in cells that use sugar as an energy source, but is most abundant in yeast, liver, muscle, and brain. The enzyme can be crystallized. Molecular weight is about 96,000 (yeast hexokinase). It can be activated by Mg²⁺, but can be blocked by HS reagents. Animal hexokinase is present as an isoenzyme.

Association with mitochondria

Hexokinases I and II can associate physically to the outer surface of the external membrane of mitochondria through specific binding to a porin, or voltage dependent anion channel. This association confers hexokinase direct access to ATP generated by mitochondria, which is one of the two substrates of hexokinase. Mitochondrial hexokinase is highly elevated in rapidly growing malignant tumor cells, with levels up to 200 times higher than normal tissues. Mitochondrially bound hexokinase has been demonstrated to be the driving force[5] for the extremely high glycolytic rates that take place aerobically in tumor cells .

Deficiency

Hexokinase deficiency is a genetic autosomal recessive disease that causes chronic haemolytic anaemia. Chronic haemolytic anaemia is caused by a mutation in the HK gene, which codes for the HK enzyme. The mutation causes a reduction of the HK activity, which causes hexokinase deficiency.