Official Full Name
Hexokinase
Background
A hexokinase is an enzyme that phosphorylates hexoses (six-carbon sugars), forming hexose phosphate. In most organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product. Hexokinase can transfer an inorganic phosphate group from ATP to a substrate. Hexokinases should not be confused with glucokinase, which is a specific isoform of hexokinase. While other hexokinases are capable of phosphorylating several hexoses, glucokinase acts with a 50-fold lower substrate affinity and its only hexose substrate is glucose.
Synonyms
Hexokinase; EC 2.7.1.1; hexokinase type IV glucokinase; hexokinase D; hexokinase type IV; hexokinase (phosphorylating); ATP-dependent hexokinase; glucose ATP phosphotransferase; ATP: D-hexose 6-phosphotransferase
Hexokinase (HK) is a transferase with low specificity. It is inhibited by glucose-6-phosphate and ADP. It has a small Km (Mie's constant) and strong affinity. It has a strong affinity for a variety of six-carbon sugars.
Figure 1. Structure of hexokinase.
Classifications
Hexokinase is known to have 4 different types, which are controlled by different genes on different chromosomes. Taking the human body as an example, 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 called glucokinase). (Note In recent years, researchers have used genomic methods to characterize the hexokinase genes in various vertebrate species and close relatives, and found that there are similar HK genes, named hexokinase domain protein 1 (HKDC1), which is believed to be the fifth type of hexokinase. The HKI and HKDC1 genes are arranged end to end, showing that they are formed by tandem gene replication events).
Figure 1. Structure of Hexokinase1.
Chemical composition
Generally speaking, the purpose of phosphorylation is to "activate" or "enable" the substrate molecule to increase its energy so that it can participate in the subsequent negative change of free energy. All kinases need to have a divalent metal ion (such as Mg2+ or Mn2+), which acts to stabilize the high-energy bond of the donor molecule and provides the possibility for phosphorylation. The largest group of kinases is protein kinases. Protein kinases act on specific proteins and change their activity. These kinases play a broad role in cell signal transduction and its complex life activities. Other different kinases act on small molecules (lipids, sugars, amino acids, nucleosides, etc.), either to send out signals or to prepare them for various biochemical reactions in metabolism. The original meaning of "kinase" is to make an enzyme that is "activated" by a substrate molecule, so it generally refers to an enzyme that transfers a phosphate group from a nucleoside triphosphate to an acceptor molecule. The acceptor molecule is activated (becomes more unstable) by obtaining energy through the transfer of this phosphate group. So many kinases need to transfer phosphate groups from NTP, but as the example cited by Jensen, kinases can sometimes transfer phosphate groups from AMP and pyrophosphate. Although generally speaking, AMP and pyrophosphate cannot be called high-energy compounds, but " "High energy" and "low energy" are relative, and there is no absolute standard. Compared with phosphorylase using inorganic phosphate as a phosphate group donor, AMP and pyrophosphate are obviously also "high energy".
Reaction process
It is an enzyme that catalyzes the phosphorylation reaction of ATP on the 6-position of hexose. The reaction process is:
Hexose ATP→Hexose-6-phosphate ADP
It has a high affinity for α-D glucose (Km=1×10-5M), and it can also phosphorylate other hexoses. The balance of this reaction shifts to the right. △G°’=4.0 kcal. This enzyme is widely present in cells that use sugar as energy source, but it is most abundant in yeast, liver, muscle, and brain. The enzyme can be crystallized. The molecular weight is about 96,000 (yeast hexokinase). It can be activated by Mg2 and K, but can be inhibited by HS reagent. Animal hexokinase exists as an isoenzyme.
In glycolysis
Glucose is unique in that it can be used by all cells to produce ATP regardless of the presence of molecular oxygen (O2). The first step of glycolysis is to phosphorylate glucose through hexokinase.
Figure 3. Glucose is phosphorylated by hexokinase.
Clinical significance
Hexokinase deficiency is an inherited autosomal recessive genetic disease that can cause chronic hemolytic anemia. Chronic hemolytic anemia is caused by mutations in the HK gene, which encodes the HK enzyme. This mutation leads to a decrease in HK activity, which leads to hexokinase deficiency.
Reference
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Robey, RB.; et al. Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene. 2006, 25 (34): 4683–96.