| dc.description.abstract | Hydrogen peroxide (H2O2) plays important roles in cell signaling and redox reactions. However,
elevated levels of H2O2 and organic peroxides induce oxidative stress, resulting in damage to
biomolecules such as DNA, proteins, and lipids. If not controlled, these damages lead to various
disorders, such as neurodegeneration, HIV activation, cardiovascular diseases, cancer, and aging.
Glutathione peroxidase (GPx) is a mammalian selenoenzyme that protects cells from oxidative
damage by mediating the reduction of peroxides utilizing glutathione (GSH) as a cofactor.
Selenium atom is incorporated into the enzyme in the form of Selenocysteine (Sec, U); the 21st
amino acid, and is present in its active site. The catalytic cycle of GPx is believed to involve
three steps. In the first step, the reduced selenolate (ESe−) moiety of Sec residue reduces
peroxides (ROOH) into water or alcohol and itself gets oxidized to selenenic acid (ESeOH),
which upon reaction with one equivalent of GSH generates a selenenyl sulfide (ESeSG)
intermediate. A second equivalent of GSH then attacks at the –Se-S- bond to regenerate the
active site selenolate and thus completes the catalytic cycle.
At high peroxide concentrations or low GSH level, the selenium center may undergo
overoxidation to produce corresponding seleninic acid (ESeO2H) and selenonic acid (ESeO3H).
Although the seleninic acid may be converted to the selenenyl sulfide by reaction with GSH, the
formation of the overoxidized selenonic acid irreversibly inactivates the enzyme, which
decreases the catalytic activity.Thus, in the overall process, two equivalents of GSH are used to
reduce one equivalent of peroxide to water or corresponding alcohol. The intracellular GSH
concentration is maintained by glutathione reductase (GR) that catalyzes the reduction of GSSG
to GSH using NADPH as cofactor.
In this thesis, synthesis, characterization and glutathione peroxidase-like activity of various
selenium-based compounds are reported | en_US |
