Glutathione (GSH) is an important antioxidant in plants, animals, fungi and some bacteria and archaea. Glutathione prevents damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides and heavy metals. It is a tripeptide having a gamma peptide bond between the carboxyl group of glutamic acid side chain and the amine group of cysteine, and the carboxyl group of cysteine is linked to glycine through a normal peptide bond.L(+)-Arginine
The thiol group is a reducing agent and is present in animal cells at a concentration of about 5 mM. Glutathione reduces disulfide bonds formed in the cytoplasm to cysteines by acting as electron donors. In this process, glutathione is converted to its oxidized form, glutathione disulfide (GSSG), also known as L - (-) - glutathione.
Once oxidized, glutathione can be reduced by glutathione reductase, using NADPH as the electron donor. The ratio of reduced intracellular glutathione to oxidized glutathione is commonly used as a measure of cellular oxidative stress.
Functions and Usages
Glutathione exists in both reduced (GSH) and oxidized (GSSG) states. In the reduced state, the sulfhydryl group of cysteine is capable of providing reducing equivalents (H ++ e-) to other molecules, such as reactive oxygen species to neutralize them, or to maintain their reduced form for the protein cysteine. By donating electrons, glutathione itself becomes reactive and easily reacts with another active glutathione to form glutathione disulfide (GSSG). This reaction is most likely due to the relatively high concentration of glutathione in cells (up to 7 mM in the liver).
In general, the interaction between GSH and other molecules with higher relative electrophilicity depletes intracellular GSH levels. An exception to this situation relates to the sensitivity of GSH to the relative concentration of electrophilic compounds. At high concentrations, the organic molecule diethyl maleate completely depletes the GSH levels in the cells. However, at low concentrations, cellular GSH levels decreased slightly and then tripled.
GSH can be regenerated from GSSG by glutathione reductase (GSR): NADPH decreases the FAD present in GSR to produce transient FADH anions. This anion then rapidly disrupts the disulfide bond (Cys58-Cys63) and causes Cys63 to nucleophilic attack the nearest sulfide unit in the GSSG molecule (promoted by His467), resulting in a mixed disulfide bond (GS-Cys58) and GS- anion . His467 of GSR then protons the GS- anion to form the first GSH. Next, Cys63 nucleophile attacks the sulfide of Cys58, releasing the GS-anion, which in turn extracts solvent protons and releases it from the enzyme, resulting in a second GSH. Thus, for each GSSG and NADPH, two reduced GSH molecules are obtained that can again act as antioxidants to scavenge reactive oxygen species in the cells.
In healthy cells and tissues, more than 90% of the total glutathione pool is reduced (GSH) and less than 10% exists as disulfide (GSSG). Increased GSSG to GSH ratio is considered an indicator of oxidative stress.
