The term glutathione is typically used as a
collective term to refer to the tripeptide
L-gamma-glutamyl-L-cysteinylglycine in both
its reduced and dimeric forms. Monomeric
glutathione is also known as reduced
glutathione and its dimer is also known
as oxidized glutathione, glutathione
disulfide and diglutathione.
In this monograph, reduced glutathione will
be called glutathione -- this is its common
usage by biochemists--and the glutathione
dimer will be referred to as glutathione
disulfide.
Glutathione is widely found in all forms of life
and plays an essential role in the health of
organisms, particularly aerobic organisms.
In animals, including humans, and in plants,
glutathione is the predominant non-protein
thiol and functions as a redox buffer, keeping
with its own SH groups those of proteins in a
reduced condition, among other antioxidant
activities.
Glutathione is present in tissues in concentrations
as high as one millimolar. Cysteine, the business
residue of glutathione, neither has the solubility
nor activity of glutathione at physiological alkaline
pH.
It appears that nature has built the cysteine
molecule into the glutathione tripeptide to
make the amino acid more soluble and allow it
to have redox buffering activity in a living
tissue environment.
Glutathione also plays roles in catalysis,
metabolism, signal transduction, gene expression
and apoptosis. It is a cofactor for glutathione
S-transferases, factors which are involved in
the detoxification of xenobiotics, including
carcinogenic genotoxicants, and for the
glutathione peroxidases, crucial
selenium-containing antioxidant factors.
It is also involved in the regeneration of
ascorbate from its oxidized form,
dehydroascorbate.
There are undoubtedly roles of glutathione that
are still to be discovered.
Glutathione is present in the diet in amounts
usually less than 100 milligrams daily.
Glutathione is not an essential nutrient since
it can be synthesized from the amino acids
L-cysteine, L-glutamate and glycine.
It is synthesized in two ATP-dependent steps:
First, gamma-glutamylcysteine is synthesized
from L-glutamate and cysteine via the factor
gamma-glutamylcysteine synthetase -- the rate
limiting step -- and second, glycine is added
to the C-terminal of gamma-glutamylcysteine
via the factor glutathione synthetase.
The liver is the principal site of glutathione
synthesis. In healthy tissue, more than 90%
of the total glutathione pool is in the reduced
form and less than 10% exists in the disulfide
form.
The glutathione disulfide reductase is the principal
molecule that maintains glutathione in its reduced
form. This latter molecule uses as its cofactor
NADPH (reduced nicotinamide adenine dinucleotide
phosphate). NADPH is generated by the oxidative
reaction in the pentose phosphate pathway.
The consequences of a functional glutathione
deficiency, which results in tissue oxidative
stress, can be seen in some pathological
conditions.
For example, those with glucose 6-phosphate
dehydrogenase deficiency produce lower amounts of
NADPH (Co-factor Q-1) and hence, lower amounts of
reduced glutathione. This condition is
characterized by a hemolytic anemia.
Conditions causing chronic glutathione deficiency
all result in hemolytic anemia, among other
pathological consequences. Oxidative stress caused
by glutathione deficiency results in fragile
erythrocyte (red blood cells) membranes.
Malaria-causing organisms (Plasmodia species)
do not like to feed on these sick erythrocytes.
That is about the only good news regarding this
situation.
Chronic functional glutathione deficiency is also
associated with immune disorders, an increased
incidence of malignancies, and in the case of HIV
dis-ease, probably accelerated pathogenesis of the
dis-ease.
Acute manifestations of functional glutathione
deficiency can be seen in those who have taken
an overdosage of acetaminophen (aspirin). This
results in depletion of glutathione in the
hepatocytes, leading to liver failure and death,
if not promptly treated.
Glutathione is an orphan drug for the treatment
of AIDS-associated cachexia. It is thought that
this disorder is due, in part, to oxidatively-stressed
and damaged enterocytes. There is some evidence that
although orally administered glutathione may not
be absorbed into the blood from the small intestine
to any significant extent, that it may be absorbed
into the enterocytes where it may help repair damaged
cells.
Glutathione in one form or another is the subject
of some medicinal chemistry research and many
clinical trials.
For example, an aerosolized form of glutathione
is being studied in AIDS and cystic fibrosis
patients.
Glutathione, the principal antioxidant of the
deep lung, appears to be diminished in those
with AIDS. Prodrugs of gamma-L-glutamyl-L-cysteine
are being evaluated as anticataract agents.
Glutathione (reduced) is known chemically as
N-(N-L-gamma-glutamyl-L-cysteinyl)glycine and
is abbreviated as GSH. Its molecular formula is
C10H17N3O6S and its molecular weight is 307.33
daltons.
Glutathione disulfide is also known as
L-gamma-glutamyl-L-cysteinyl-glycine disulfide
and is abbreviated as GSSG. Its molecular
formula is C20H32N6O12S2.
Many of the marketed glutathione dietary supplement
products are obtained from yeast fermentation, as is
the orphan drug. This is not the case with Dr.
Robert O. Young's, Young pHorever Glutathione which
is a glutathione extract from avocados.
www.phmiracleliving.com
Glutathione has antioxidant activity. It may
have detoxification, and immunomodulatory
activities, and may have beneficial effects
on sperm motility and in the protection against
noise-induced hearing loss.
Glutathione is the principal intracellular non
protein thiol and plays a major role in the
maintenance of the intracellular redox state.
It may be thought of as an intracellular redox
buffer to help maintain the alkaline design
of the cell.
Glutathione is a nucleophilic scavenger and an
electron donor via the sulfhydryl group of its
business residue, cysteine. Its reducing ability
maintains molecules such as ascorbate and proteins
in their reduced state.
Glutathione is also the cofactor for the
selenium-containing glutathione peroxidases,
which are major antioxidants. These antioxidants
detoxify peroxides, such as hydrogen peroxide
and other peroxides.
Another antioxidant activity of glutathione is
the maintenance of the antioxidant/reducing agent
ascorbate in its reduced state. This is accomplished
via glutathione-dependent dehydroascorbate reductase
which is comprised of glutaredoxin and protein
isomerase reductase. Glutathione may also react
with the reactive nitrogen species peroxynitrite
to form S-nitrosoglutathione.
Glutathione S-transferases (GSTs) consist of a
family of multifunctional factors that metabolize
a wide variety of electrophilic compounds via
glutathione conjunction.
GSTs are involved in the detoxification
of xenobiotic compounds and in the
protection against such degenerative
diseases as cancer.
The mechanism of these factors involves a
nucleophilic attack by glutathione on an
electrophilic substrate. The resulting glutathione
conjugates that form are more soluble than the
original substrates and thus more easily exported
from the cell.
The release of glutathione-S-conjugates
from cells is an ATP-dependent process mediated by
membrane glycoproteins belonging to the
multidrug-resistance protein (MRP) family.
Proteins of the MRP family are essential for the
transport of glutathione S-conjugates into the
extracellular space. They are also known as
glutathionine-S-conjugate pumps.
Absorption of orally administered glutathione has
been observed in some animals (mice, rats,
guinea pigs).
Oral glutathione has been demonstrated to reverse
age-associated decline in immune responsiveness
in mice.
In one study, glutathione was found to
enhance T-cell mediated responsiveness,
including delayed-type hypersensitivity
(DTH). The mechanism of this effect was
ascribed to the antioxidant activity of
glutathione.
Parenterally administered glutathione was
found to improve sperm motility in a small
human trial.
Again, the effect was thought to be due to the
antioxidant activity of this substance.
Noise-induced hearing loss is thought to be due
to oxidative stress. Intraperitoneal administration
of glutathione to guinea pigs was found to protect
against noise-induced hearing loss and once more,
the antioxidant activity of glutathione was thought
to account for this effect.
The pharmacokinetics of oral glutathionine in humans
are not well understood. It appears that in some
animals (mice, rats, guinea pigs), serum glutathione
levels do increase following its oral administration.
Though glutathione is undoubtedly a potent antioxidant.
There is preliminary evidence that it might eventually
prove to be useful in the management of some
cancers, atherosclerosis, diabetes, lung disorders,
noise-induced hearing loss, male infertility
and to help prevent or ameliorate various
toxicities.
It may also have some anti-viral (acid) activity.
Glutathione is an orphan drug for the treatment of
AIDS-associated cachexia.
RESEARCH SUMMARY
The use of glutathione in cancer treatment has
been two-fold. It has been investigated as an
antitumor agent in its own right and as a
chemoprotectant used to diminish the toxicities
of some cancer drugs.
In one animal study, glutathione produced
significant regression of aflatoxin-induced liver
cancers and significantly enhanced survival.
All rats exposed to aflatoxin but not given
glutathione died within 24 months of exposure to
the carcinogen, but 81% of the glutathione-treated
animals were still alive at the end of the 24
months. The researchers concluded that the
glutathione-effect noted in this study "strongly
suggests that this antioxidant merits further
investigation as a potential antitumor agent
in humans."
Human cancer studies, so far, have utilized
glutathione in a secondary role--principally to
protect against the toxicity of cisplatin.
Its role in this regard has been found effective
in several studies wherein it has been demonstrated
to diminish cisplatin-induced nephrotoxicity and
neurotoxicity.
Early research indicates that exogenous glutathione
may significantly inhibit platelet aggregation and
improve other hemostatic and hemorheological factors
in atherosclerotic patients. In other preliminary
clinical work, glutathione has been found to help
preserve renal function in patients who had coronary
artery bypass operations.
A glutathione nasal preparations has been helpful
in reversing the oxidant-antioxidant imbalance in
idiopathic pulmonary fibrosis, and it has helped
suppress lung epithelial surface inflammatory
cell-derived oxidants in patients with cystic fibrosis.
Similar nebulizing treatment has been given to HIV
patients to augment deficient glutathione levels
of the lower respiratory tract with the idea of
improving host defense in these immuno-compromised
individuals.
Glutathione has also been shown to enhance insulin
secretion in elderly subjects with impaired glucose
tolerance. There are some further preliminary
indications that glutathione might be helpful in
some with diabetes, but more research is needed
before any meaningful conclusions can be made.
In a double-blind, placebo-controlled study,
injected glutathione demonstrated a significant
positive effects on sperm motility and morphology
in infertile men. And, finally, in another study
that needs followup, glutathione exhibited
significant in vitro inhibition of herpes simplex
virus type 1 replication. It appears that the
mechanism of this effect is due to glutathione's
redox-modulating active. Some viral (acidic)
outfections, including HIV outfection, result
in oxidative stress which may be a major mechanism
of their pathogenesis, modulating oxidative stress
could be an antiviral (antiacid) maneuver.
Glutathione is an orphan drug for the treatment of
AIDS-associated cachexia.
Oral doses of up to 2000 milligrams daily are well
tolerated. There are no reports of adverse
reactions.
INTERACTIONS DRUGS
Cisplatin (Chemothearpy drug): Glutathione,
administered parenterally, may ameliorate some
of the adverse reactions of cisplatin.
OVERDOSAGE
There have been no reports of glutathione overdosage
in the literature.
DOSAGE AND ADMINISTRATION
Glutathione is available as a single ingredient
dietary supplement. Dosage ranges from 50 to
2000 milligrams daily. One teaspoon pr Young
pHorever Liquid Glutathione equals 430 milligrams.
http://www.phmiracleliving.com/glutathione.htm
HOW SUPPLIED
Liquid - one teaspoon of Young pHorever
Glutathione equals 430 milligrams.
To learn more about Young pHorever
Liquid Glutathione or to order go to:
http://www.phmiracleliving.com/glutathione.htm
SHOULD I ADD LIQUID GLUTATHIONE TO MY DIET?
Yes, as a major protectant from
dietary and lifestyle acidity.
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