Glutathione
(GSH)
Master Antioxidant and Cellular Detoxifier
Mammalian
cells have evolved numerous mechanisms to prevent or treat injurious
events that can result from normal oxidative by-products of cellular
metabolism (oxiradicals). Glutathione
(GSH) is a tripeptide, found
in human cell tissue, formed from
the amino acids cysteine,
glycine, and glutamic acid.
The
"glutathione antioxidant system"
is foremost among these internal protective systems because glutathione
participates directly in the destruction of reactive oxygen compounds.
Glutathione
destroys free radicals, is involved in the detoxification of foreign
compounds such as carcinogens, etc., and supports the normal active
functioning of the immune
system. It is our
body's Master Antioxidant.
As
an antioxidant, glutathione is essential for allowing white
blood cells (or lymphocytes) to express their
full potential, without being hampered
by oxyradical accumulation during the oxygen requiring development
of the immune response.
As
glutathione levels drop, the person gets sicker. This is because
white blood cells and the liver use GSH to detoxify poisons inside
the body. When the level decreases, less toxins are able to be
eliminated leading to a build up in the body. This leads to increased
white blood cell death (due to the cell poisoning itself) and
liver impairment.
Glutathione
is also required to detoxify the nicotine and free-radicals contained
in cigarette smoke - even second hand smoke. It is effective against
the toxins contained in the exhaust fumes of motor vehicles and
also against pesticides and other environmental toxins.
Glutathione
plays a key role in the body’s defense against pollutants and
ultraviolet radiation. Removal
of heavy metals (mercury, lead, cadmium) from the body requires
glutathione. When these toxins combine with glutathione, they
form a water soluble compound that can be excreted once and for
all by the kidneys.
The
highest concentration of glutathione is found in the liver which
is the principal organ involved in the detoxification and elimination
of toxic materials. Interestingly, glutathione also acts to reconstitute
vitamins C and E after they have been oxidized, and therefore
plays a determinant role in their function.
Glutathione
plays an important role in cancer
prevention and treatment. GSH loss or low glutathione
levels are implicated in immune compromised individuals, neuro-degenerative
diseases such as Multiple Sclerosis,
ALS, Alzheimers, and Parkinsons
disease, atherosclerosis, hydroxylradical formation, cataracts,
damage from many pharmaceutical drugs, cancer and poor survival
rates for victims of AIDS.
The Glutathione Antioxidant system
The
"glutathione antioxidant system" is among your body's
most important internal protective systems because glutathione
participates directly in the destruction of reactive oxygen compounds
(free
radicals or oxiradicals) -
the normal
oxidative by-products of cellular metabolism.
Glutathione
destroys free radicals, is involved in the detoxification of foreign
compounds such as carcinogens, etc., and supports the normal active
functioning of the immune
system.
In
the Glutathione
Oxidation Reduction (Redox) Cycle, one molecule of (harmful)
hydrogen peroxide is reduced to 2 molecules of (harmless) water,
while 2 molecules of (reduced) glutathione (GSH) are oxidized
in a reaction catalyzed by the enzyme, glutathione peroxidase,
which requires selenium as a catalyst.
Hence,
GSH is transformed to GSSG. The
ratio of GSSG/GSH in the cell is an important marker of oxidative
stress. Glutathione
reduces toxic substances before they can damage other molecules
or important parts of the cell.
When
these toxins combine with glutathione, they form a water soluble
compound that can be excreted once and for all by the kidneys.
The highest concentration of glutathione is found in the liver
which is the principal organ involved in the detoxification and
elimination of toxic materials.
See
also:
Glutathione:
Systemic Protectant Against Oxidative and Free Radical Damage
Parris M. Kidd, Ph.D.
Glutathione
metabolism and its implications for health
Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. [J Nutr.
2004 Mar;134(3):489-92.]
Glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) is the most
abundant low-molecular-weight thiol, and GSH/glutathione disulfide
is the major redox couple in animal cells. The synthesis of GSH
from glutamate, cysteine, and glycine is catalyzed sequentially
by two cytosolic enzymes, gamma-glutamylcysteine synthetase and
GSH synthetase. Compelling evidence shows that GSH synthesis is
regulated primarily by gamma-glutamylcysteine synthetase activity,
cysteine availability, and GSH feedback inhibition. Animal and
human studies demonstrate that adequate protein nutrition is crucial
for the maintenance of GSH homeostasis. In addition, enteral or
parenteral cystine, methionine, N-acetyl-cysteine, and L-2-oxothiazolidine-4-carboxylate
are effective precursors of cysteine for tissue GSH synthesis.
Glutathione plays important roles in antioxidant defense, nutrient
metabolism, and regulation of cellular events (including gene
expression, DNA and protein synthesis, cell proliferation and
apoptosis, signal transduction, cytokine production and immune
response, and protein glutathionylation). Glutathione deficiency
contributes to oxidative stress, which plays a key role in aging
and the pathogenesis of many diseases (including kwashiorkor,
seizure, Alzheimer's disease, Parkinson's disease, liver disease,
cystic fibrosis, sickle cell anemia, HIV, AIDS, cancer, heart
attack, stroke, and diabetes). New knowledge of the nutritional
regulation of GSH metabolism is critical for the development of
effective strategies to improve health and to treat these diseases.
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