Glutathione

Glutathione (GSH) is a tripeptide. It contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side chain. Glutathione, an antioxidant, protects cells from toxins such as free radicals.
Thiol groups are kept in a reduced state within ~5 mM in animal cells. In effect, glutathione reduces any disulfide bonds formed within cytoplasmic proteins to cysteines by acting as an electron donor. Glutathione is found almost exclusively in its reduced form, since the enzyme which reverts it from its oxidized form (GSSG), glutathione reductase, is constitutively active and inducible upon oxidative stress. In fact, the ratio of reduced to oxidized glutathione within cells is often used scientifically as a measure of cellular toxicity.

Biosynthesis
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 adenosine triphosphate-dependent steps:
first, gamma-glutamylcysteine is synthesized from L-glutamate and cysteine via the enzyme gamma-glutamylcysteine synthetase (a.k.a. glutamate cysteine ligase, GCL). This reaction is the rate limiting step in glutathione synthesis.
second, glycine is added to the C-terminal of gamma-glutamylcysteine via the enzyme glutathione synthetase.
Glutamate cysteine ligase (GCL) is a heterodimeric enzyme comprised of a catalytic (GCLC) and modulatory (GCLM) subunit. GCLC constitutes all the enzymatic activity, while GCLM increases the catalytic efficiency of GCLC. Mice lacking GCLC (ie all de novo GSH synthesis) die before birth.[2] Mice lacking GCLM demonstrate no outward phenotype but exhibit marked decrease in GSH and increased sensitivity to toxic insults.
The liver is the principal site of glutathione synthesis. Following birth, mice with genetically-induced loss of GCLC (ie GSH synthesis) only in the liver die within 1 month of birth.
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 (GSSG). An increased GSSG/GSH ratio is considered indicative of oxidative stress.

Function
Glutathione participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It is also important as a hydrophilic molecule that is added to lipophilic toxins and waste in the liver during biotransformation before they can become part of the bile. Glutathione is also needed for the detoxification of methylglyoxal, a toxin produced as a by-product of metabolism. This detoxification reaction is carried out by the glyoxalase system. Glyoxalase I (EC 4.4.1.5) catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II (EC 3.1.2.6) catalyzes the hydrolysis of S-D-Lactoyl-glutathione to glutathione and D-lactate.

GSH is known as a substrate in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in cytosol, microsomes, and mitochondria. However, it is also capable of participating in non-enzymatic conjugation with some chemicals, as in the case of n-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450-reactive metabolite formed by paracetamol (or acetaminophen as it is known in the US), that becomes toxic when GSH is depleted by an overdose of acetaminophen. Glutathione in this capacity binds to NAPQI as a suicide substrate and in the process detoxifies it, taking the place of cellular protein thiol groups which would otherwise be covalently modified; when all GSH has been spent, NAPQI begins to react with the cellular proteins, killing the cells in the process. The preferred treatment for an overdose of this painkiller is the administration (usually in atomized form) of N-acetylcysteine, which is used by cells to replace spent GSSG and renew the usable GSH pool.


Supplementation
Supplementing has been difficult as research suggests that glutathione taken orally is not well absorbed across the GI tract. In a study of acute oral administration of a very large dose (3 grams) of oral glutathione, Witschi and coworkers found that "it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione."However glutathione precursors such as undenatured whey protein , and N-acetyl-cysteine have been shown to increase glutathione content within the cell. N-acetylcysteine is a generically available supplement which has been demonstrated to increase intracellular reduced and total glutathione by 92% and 58% respectively.


Pathology
Excess glutamate at synapses, which may be released in conditions such as traumatic brain injury, can prevent the uptake of cysteine, a necessary building block of glutathione. Without the protection from oxidative injury afforded by glutathione, cells may be damaged or killed

reference: http://en.wikipedia.org/wiki/Glutathione



Most of the popular glutathione products approved by BFAD in the Philippines is Lucida-DS and Metathione, Lucida- DS ( around P1500) seemed to be cheap since it claims that it contains 500mg of Glutathione per capsule while Metathione (over P2000) only has 125 mg Glutathione per capsule. Its up to you on what you want to buy.