Glutathione exists in both reduced (GSH) and oxidized (GSSG)
states. In the reduced state, the thiol group of cysteine is able
to donate areducing equivalent(H++ e) to other unstable molecules, such as reactive oxygen species.
In donating an electron, glutathione itself becomes reactive, but
readily reacts with another reactive glutathione to formglutathione
disulfide(GSSG). Such a reaction is probable due to the relatively
high concentration of glutathione in cells (up to 5 mM in the
GSH can be regenerated from GSSG by the enzymeglutathione
reductase(GSR):NADPH reduces FAD present in GSR to produce a
transient FADH-anion. This anion then quickly breaks a disulfide
bond (Cys58 - Cys63) and leads to Cys63's nucleophilically
attacking the nearest sulfide unit in the GSSG molecule (promoted
by His467), which creates a mixed disulfide bond (GS-Cys58) and a
GS-anion. His467 of GSR then protonates the GS-anion to form the
first GSH. Next, Cys63 nucleophilically attacks the sulfide of
Cys58, releasing a GS-anion, which, in turn, picks up a solvent
proton and is released from the enzyme, thereby creating the second
GSH. So, for every GSSG and NADPH, two reduced GSH molecules are
gained, which can again act as antioxidants scavenging reactive
oxygen species in the cell.
In healthy cells and tissue, more than 90% of the total glutathione
pool is in the reduced form (GSH) and less than 10% exists in the
disulfide form (GSSG). An increased GSSG-to-GSH ratio is considered
indicative ofoxidative stress.
Glutathione has multiple functions:
- It is the major endogenous antioxidant produced by the cells,
participating directly in the neutralization of free radicals and
reactive oxygen compounds, as well as maintaining exogenous
antioxidants such as vitamins C and E in their reduced (active)
- Regulation of thenitric oxidecycle, which is critical for life but
can be problematic if unregulated
- It is used in metabolic and biochemical reactions such as DNA
synthesis and repair, protein synthesis, prostaglandin synthesis,
amino acid transport, and enzyme activation. Thus, every system in
the body can be affected by the state of the glutathione system,
especially the immune system, the nervous system, the
gastrointestinal system and the lungs.
- It has a vital function in iron metabolism. Yeast cells depleted of
or containing toxic levels of GSH show an intense iron
starvation-like response and impairment of the activity of
extra-mitochondrial ISC enzymes, followed by death.