[Glutatione transferases--structure and functions. beta-lyase-dependent bioactivation of cysteine S-conjugates].
Glutathione transferases (GSTs) catalyze nucleophilic attack of glutathione on electrophilic center of the second substrate, hydrophobic in character. It leads to the formation of glutathione S-conjugates (thioethers), which are subsequently eliminated from the organism as mercapturic acids. However, in some reactions, glutathione can also fulfills the role of a cofactor, facilitating transformation of a hydrophobic substrate molecule, and released after the structure has been changed. Glutathione transferases participate in the processes of conjugation, reduction, isomerization, synthesis of sex hormones, prostaglangins and leukotrienes, degradation of aromatic compounds and signal transduction. The role of these enzymes consists principally in increasing glutathione nucleophilicity by its appropriate positioning and binding in active center, and its following activation by catalytic amino acid residues. There are also so-called ligandins, i.e. glutathione transferases which can bind hydrophobic, non-substrate ligands, thereby contributing to their sequestration. GSTs play a dominating role in detoxification of xenobiotics eliminated from the body in the form of thioethers, which however, under certain conditions, can be bioactivated in beta-liase-catalyzed reaction to form compounds capable of forming tissue adducts. Inhibition of S-transferase activity can have therapeutic significance both when thioethers are activated by beta-liase and during carcinogenesis, which is often accompanied by overexpression of GSTs.
Sokołowska-Jezewicz
Maria
M
Jagiellonian University, Medical College, Faculty of Medicine, 7 Kopernika St., 31-034 Kraków, Poland.
Kryczyk
Agata
A
Dudzik
Paulina
P
Włodek
Lidia
L
D002384:Catalysis; D003543:Cysteamine / Q000031:analogs & derivatives / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry* / Q000378:metabolism*; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis; D015289:Leukotrienes / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000502:physiology; D008190:Lyases / Q000378:metabolism; D008958:Models, Molecular; D011453:Prostaglandins / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology
D012739:Gonadal Steroid Hormones; D015289:Leukotrienes; D011453:Prostaglandins; C017161:cysteamine-S-phosphate; D003543:Cysteamine; D005982:Glutathione Transferase; D008190:Lyases