GLUTATHIONE

Dela Rosa, V. Garcia, A. Gueco, M.

Ducut, C. Garcia, N. Guevarra, A.
Dula, J. Garcia, T. Guevarra, S.
Dungao, C. Garfin, A. Guieb, M.
Esteban, I. Gonzalez, K. Gunnacao, J.
Gaor, C. Gozun, K.
 What is Glutathione?
• Glutathione (GSH) is the body’s own master antioxidant discovered way
back in 1889
• It is an important antioxidant that prevents damage to important cellular
components caused by reactive oxygen species (e.g. free radicals, peroxides,
lipid peroxides and heavy metals)
 Biochemistry of Glutathione
• Reduced glutathione (GSH) is a linear tripeptide of L-glutamine, L-cysteine, and glycine
• AKA: N-L-gamma-glutamyl-cysteinyl glycine or L-glutathione
• Sulfhydryl (SH) group on the cysteinyl portion = strong electron-donating character
• As electrons are lost, the molecule becomes oxidized
• Two oxidized molecules link (dimerize) reversibly by an S-S bridge to form glutathione
disulfide or oxidized glutathione (GSSG)
• GSH is under tight homeostatic control both intracellularly and extracellularly. A
dynamic balance is maintained between GSH synthesis, its recycling from GSSG, and its
utilization.
 Metabolism of Glutathione
• GSH synthesis involves two closely linked, enzymatically-controlled reactions that
utilize ATP
1. Cysteine and glutamate are combined by gamma-glutamyl cysteinyl synthetase
2. Gamma-glutamylcysteine and glycine are combined by GSH synthetase to
generate GSH
• As GSH levels rise, they self-limit further GSH synthesis; otherwise, cysteine
availability is usually rate-limiting
• Fasting, protein-energy malnutrition, or other dietary amino acid deficiencies limit
GSH synthesis
 Metabolism of Glutathione
• GSH is transported out of the cell and broken down by:
1. Membrane-bound enzyme gamma-GT, which removes the gamma-glutamyl moiety
2. Dipeptidases, which remove the glycine moiety

• The resulting amino acids can be reabsorbed and used for additional GSH synthesis
• GSH recycling is catalyzed by glutathione disulfide reductase, which uses
reducing equivalents from NADPH to reconvert GSSG to 2GSH
• The reducing power of ascorbate helps conserve systemic GSH
 MOA of Glutathione
• Cell protectant - directly quenches reactive hydroxyl free radicals, other oxygen-
centered free radicals, and radical centers on DNA and other biomolecules. GSH is a
primary protectant of skin, lens, cornea, and retina against radiation damage and
other biochemical foundations of P450 detoxification.
• Essential cofactor - for many enzymes that require thiol-reducing equivalents, and
helps keep redox-sensitive active sites on enzyme in the necessary reduced state.
• Energetics and neurotransmitter syntheses - GSH availability down-regulates the
pro-inflammatory potential of leukotrienes and other eicosanoids. Recently
discovered S-nitroso metabolites, generated in vivo from GSH and NO (nitric
oxide), further diversify GSH's impact on metabolism.
 Roles of Glutathione
• Regulation of cell growth and
division
• DNA synthesis and repair
• Protein synthesis
• Amino acid transport
• Enzyme catalysis
• Enzyme activation
• Metabolism of toxins
• Metabolism of carcinogens
• Metabolism of xenobiotics
• Enhancement of systemic immune
function
• Enhancement of humoral immune function
• Resistance to UV radiation
• Decreases radiation damage
• Decreases free radical damage
• Decreases oxyradical damage
• Metabolism of H2O2
• Recycling of other antioxidants (master
antioxidant role)
• Storage and transport of cysteine
• Regulation of homocysteine
 What does Glutathione do to our bodies?
• Antioxidant - the body depends on GSH for the removal of toxins, therefore
playing a major role in immune functions. Other antioxidants in the body depend
on GSH to function properly.
• Detoxification - binding to pollutants such as carcinogens, heavy metals,
herbicides, pesticides and radiation by forming a soluble compound with the toxin
that can then be excreted through the urine or bile.
• Immune system - Healthy growth and activity of immune cells depends on the
availability of GSH. Low GSH levels are seen in many diseases such as AIDS,
advanced diabetes, and cancers.
 What does Glutathione do to our bodies?
• Increased Energy - GSH enables the mitochondria to remain fully charged,
enhancing muscle strength and endurance. Clinical trials have shown that lowering
GSH in the mitochondria results in cell death.
• Repair - Free radicals attack the nearest stable molecule, "stealing" its electron. A
molecule that loses an electron then becomes a free radical itself and attacks the
next nearest stable molecule, leading to a chain reaction, causing a cell to eventually
die or mutate. GSH repairs the damaged DNA by replacing the missing electron.
• Indicator of Oxidative Stress - Glutathione exists in reduced (GSH) and oxidized
(GSSG) states. Normally, more than 90% of the total Glutathione is GSH form and
less than 10% is GSSG. An increased GSSG/GSH ratio may indicate oxidative
stress, therefore measuring the extent of cellular toxicity.
 References
• http://www.webmd.com/vitamins-supplements/ingredientmono-717-
glutathione.aspx?activeingredientid=717&activeingredientname=glutathione
• http://www.maxusateam.com/nutritional-supplements/what-is-
glutathione.html
• http://www.immunehealthscience.com/glutathione.html
• http://www.essentialgsh.com/glutathione.html
• http://pharmrev.aspetjournals.org/content/50/3/335/F1.expansion