GST Enzymatic functions
GST Enzymatic functions
Professor-Dr- Qutaiba Farhan Dawood-Department of Chemstry
esp.kutayba.farhan.dawood@uoanbar.edu.iq
GSTs display multifunctional nature because they are involved in different types of processes and have different enzyme activities. The main function is the transferase activity i.e. the reaction of conjugation of GSH to a wide variety of hydrophobic compounds, endobiotics or xenobiotics (Fig. 1) that have an electrophilic center. These electrophilic substrates include epoxides, alkyl and aryl halides, esters, activated alkenes, quinones and α, β-unsaturated carbonyls compounds. With this conjugation the glutathione transferase plays the function of detoxification against of toxic compounds, both of endogenous nature, such as secondary metabolites of oxidative stress, both of exogenous nature, such as drugs, carcinogens, environmental pollutants, pesticides and herbicides. In addition to this specific activity, some isoforms also show a glutathione peroxidase selenium-independent activity, allowing them to catalyze the reduction of lipid hydroperoxide in the corresponding alcohols.
Examples of conjugation, reduction, thiolysis, and isomerization reactions catalyzed by GST. The following substrates are shown: (a) chlorodinitrobenzene, (b) 4-nitrophenyl acetate, (c) sulforaphane (d) trinitroglycerin, (e) cumene hydroperoxide, (f) maleylacetoacetate, (g) prostaglandin PGH2.
Thanks to this activity of peroxidation, combined with that of conjugation, the GSTs play an important role in the tissue protection process against oxidative damage. Other isoenzymes show an additional isomerase activity to various compounds such as unsaturated D5-3-chetosteroid, maleylacetoacetic acid and maleylacetone (Fig. 1). GSTs are also able to bind endogenous compounds such as leukotrienes and prostaglandins acting both in their catabolism, through the classic reaction of conjugation with the GSH (Fig. 2), and in their process of biosynthesis. As an example of enzymatic mechanism is reported below the conjugation of GSH to the universal co-substrate 1-chloro-2,4-dinitrobenzene (CDNB):
The catalysis of nucleophilic aromatic substitution reactions can be divided into steps involving binding of substrates to the enzyme active site, activation of GSH by deprotonation of the thiol to form the nucleophilic thiolate, and nucleophilic attack by the thiolate at the electrophilic center to form a σ-complex.