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.
