Glutathione S-Transferase

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Glutathione S-transferase is the key enzyme in the glutathione binding reaction. It catalyzes the initial step of the glutathione binding reaction and mainly exists in the cytosol.

Figure 1. Protein structure of Glutathione S-transferase.

Classifications

According to different substrates, it can be divided into at least the following 5 types:

1. Glutathione S-alkyltransferase: catalyzes the glutathione binding reaction of alkyl halides and nitroalkanes. Mainly in the liver and kidneys.
2. Glutathione S-aryl transferase: mainly catalyzes the glutathione binding reaction of aromatic hydrocarbons or other cyclic compounds containing halogen or nitro groups, such as bromobenzene and organophosphorus pesticides. The enzyme mainly exists in the cytosol of the liver.
3. Glutathione S-aralkyltransferase: catalyzes the glutathione binding reaction of aralkyl groups, for example, aralkyl halides such as benzyl chloride. Mainly in the liver and kidneys.
4. Glutathione S-epoxide transferase: It catalyzes the combination of epoxide derivatives of aromatic hydrocarbons and halogenated benzene compounds with glutathione, mainly in the cytosol of liver and kidney.
5. Glutathione S-alkene transferase: It catalyzes the binding reaction of unsaturated olefin compounds containing α, β-unsaturated carbonyl groups with glutathione, mainly in the cytosol of liver and kidney.

Functions

The activity of GST depends on the stable supply of GSH from the synthetases γ-glutamylcysteine synthetase and glutathione synthetase, and the role of specific transporters to remove GSH conjugates from the cell. The main role of GST is to detoxify the heterologous by catalyzing the nucleophilic attack of GSH on the electrophilic carbon, sulfur or nitrogen atoms of the non-polar heterologous substrate, thereby preventing their interaction with key cellular proteins and nucleic acids. Specifically, the function of GST in this role is twofold: it binds to the substrate of the hydrophobic H site of the enzyme and the GSH of the adjacent hydrophilic G site, and the two together form the active site of the enzyme; Then the sulfhydryl group of GSH is activated, thereby nucleophilic attack on the substrate. Glutathione molecules bind in the gap between the N-terminal and C-terminal domains-catalytically important residues are proposed to reside in the N-terminal domain. The two subunits of the GST dimer, whether heterodimer or homodimer in nature, contain a non-substrate binding site and a GSH binding site. However, in heterodimeric GST complexes, such as those formed by cytoplasmic mu and α, the gap between the two subunits is the location of another high-affinity non-substrate heterologous biological binding site This may explain the ability of the enzyme to form heterodimers.

Clinical significance

Abnormal result:

• In acute hepatitis, CST changes are positively correlated with ALT;
• In severe hepatitis and chronic hepatitis, there are significantly more people with elevated GST than those with elevated ALT;
• Severe hepatitis patients, serum CST is significantly increased, most of which are 5-8 times that of normal people;
• The GST of patients with acute severe hepatitis sometimes rises to several tens of times the normal value.
• People who need to be checked: patients suspected of hepatitis or judgment of hepatitis.