12/10/2012
Gluthathione whitening pills
This gluthathione is awesome antioxidant for us and as well whitening pills.
Glutathione (GSH) is a tripeptide with a gamma peptide linkage between the amine group of cysteine (which is attached by normal peptide linkage to a glycine) and the carboxyl group of the glutamate side-chain. It is an antioxidant, preventing damage to important cellular components caused by reactive oxygen species such as free radicals and peroxides.[2]
Thiol groups are reducing agents, existing at a concentration of approximately 5 mM in animal cells. Glutathione reduces disulfide bonds formed within cytoplasmic proteins to cysteines by serving as an electron donor. In the process, glutathione is converted to its oxidized form glutathione disulfide (GSSG), also called L(-)-Glutathione.
Once oxidized, glutathione can be reduced back by glutathione reductase, using NADPH as an electron donor. The ratio of reduced glutathione to oxidized glutathione within cells is often used as a measure of cellular toxicity.[3]
Contents
[hide]
• 1 Biosynthesis
• 2 Function
o 2.1 Function in animals
o 2.2 Function in plants
• 3 Supplementation
o 3.1 Cancer
• 4 Pathology
• 5 Methods to determine glutathione
• 6 Importance in winemaking
• 7 See also
• 8 References
• 9 Related research
• 10 External links
[edit]Biosynthesis
Glutathione is not an essential nutrient (meaning it does not have to be obtained via food), since it can be synthesized in the body from the amino acids L-cysteine, L-glutamic acid, and glycine. The sulfhydryl (thiol) group (SH) of cysteine serves as a proton donor and is responsible for the biological activity of glutathione. Cysteine is the rate-limiting factor in cellular glutathione synthesis, since this amino acid is relatively rare in foodstuffs.
Glutathione 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.[4]
Second, glycine is added to the C-terminal of gamma-glutamylcysteine via the enzyme glutathione synthetase.
Animal glutamate cysteine ligase (GCL) is a heterodimeric enzyme composed of a catalytic (GCLC) and modulatory (GCLM) subunit. GCLC constitutes all the enzymatic activity, whereas GCLM increases the catalytic efficiency of GCLC. Mice lacking GCLC (i.e., lacking all de novoGSH synthesis) die before birth.[5] Mice lacking GCLM demonstrate no outward phenotype, but exhibit marked decrease in GSH and increased sensitivity to toxic insults.[6][7][8]
While all cells in the human body are capable of synthesizing glutathione, liver glutathione synthesis has been shown to be essential. Mice with genetically-induced loss of GCLC (i.e., GSH synthesis) only in the liver die within 1 month of birth.[9]
The plant glutamate cysteine ligase (GCL) is a redox-sensitive homodimeric enzyme, conserved in the plant kingdom.[10] In an oxidizing environment, intermolecular disulfide bridges are formed and the enzyme switches to the dimeric active state. The midpoint potential of the critical cysteine pair is -318 mV. In addition to the redox-dependent control is the plant GCL enzyme feedback inhibited by GSH.[11] GCL is exclusively located in plastids, and glutathione synthetase is dual-targeted to plastids and cytosol, thus are GSH and gamma-glutamylcysteine exported from the plastids.[12] Both glutathione biosynthesis enzymes are essential in plants; knock-outs of GCL and GS are lethal to embryo and seedling.[13]
The biosynthesis pathway for glutathione is found in some bacteria, like cyanobacteria and proteobacteria, but is missing in many other bacteria. Most eukaryotes synthesize glutathione, including humans, but some do not, such as Leguminosae, Entamoeba, and Giardia. The only archaea that make glutathione are halobacteria.[14][15]
[edit]Function
Glutathione exists in reduced (GSH) and oxidized (GSSG) states. In the reduced state, the thiol group of cysteine is able to donate a reducing 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 form glutathione disulfide (GSSG). Such a reaction is probable due to the relatively high concentration of glutathione in cells (up to 5 mM in the liver).
GSH can be regenerated from GSSG by the enzyme glutathione 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 of oxidative 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) forms.[16]
Regulation of the nitric oxide cycle, which is critical for life but can be problematic if unregulated[17]
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.[18]
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.[19]
[edit]Function in animals
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.
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), which becomes toxic when GSH is depleted by an overdose of acetaminophen, glutathione is an essential antidote to overdose. Glutathione conjugates to NAPQI and helps to detoxify it. In this capacity, it protects cellular protein thiol groups, which would otherwise become 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-acetyl-L-cysteine (often as a trademarked preparation called Mucomyst[1]), which is processed by cells to L-cysteine and used in the de novo synthesis of GSH.
Glutathione (GSH) 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-lactic acid.
Glutathione has recently been used as an inhibitor of melanin in the cosmetics industry. In countries like Japan and the Philippines, this product is sold as a whitening soap. Glutathione competitively inhibits melanin synthesis in the reaction of tyrosinase and L-DOPA by interrupting L-DOPA's ability to bind to tyrosinase during melanin synthesis. The inhibition of melanin synthesis was reversed by increasing the concentration of L-DOPA, but not by increasing tyrosinase. Although the synthesized melanin was aggregated within 1 h, the aggregation was inhibited by the addition of glutathione. These results indicate that glutathione inhibits the synthesis and agglutination of melanin by interrupting the function of L-DOPA."[20]
[edit]Function in plants
In plants, glutathione is crucial for biotic and abiotic stress management. It is a pivotal component of the glutathione-ascorbate cycle, a system that reduces poisonous hydrogen peroxide.[21] It is the precursor of phytochelatins, glutathione oligomeres that chelate heavy metals such as cadmium.[22] Glutathione is required for efficient defence against plant pathogens such asPseudomonas syringae and Phytophthora brassicae.[23] APS reductase, an enzyme of the sulfur assimilation pathway uses glutathione as electron donor. Other enzymes using glutathione as substrate are glutaredoxin, these small oxidoreductases are involved in flower development, salicylic acid and plant defence signalling.[24]
[edit]Supplementation
Raising GSH levels through direct supplementation of glutathione is difficult. Research suggests that glutathione taken orally is not well absorbed across the gastrointestinal tract. In a study of acute oral administration of a very large dose (3 grams) of oral glutathione, Witschi and coworkers found "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."[25][26] However, it is possible to increase and maintain appropriate Glutathione levels by increasing the daily consumption of Cysteine-rich foods and/or supplements.
Calcitriol, the active metabolite of vitamin D synthesized in the kidney, increases glutathione levels in the brain and appears to be a catalyst for glutathione production.[27]
In addition, plasma and liver GSH concentrations can be raised by administration of certain supplements that serve as GSH precursors. N-acetylcysteine, commonly referred to as NAC, is the most bioavailable precursor of glutathione.[28] Other supplements, including S-adenosylmethionine (SAMe)[29][30][31] and whey protein[32][33][34][35][36][37] have also been shown to increase glutathione content within the cell.
NAC is available both as a drug and as a generic supplement. Alpha lipoic acid has also been shown to restore intracellular glutathione.[38][39] Melatonin has been shown to stimulate a related enzyme, glutathione peroxidase,[40] and silymarin, an extract of the seeds of the milk thistle plant (Silybum marianum), has also demonstrated an ability to replenish glutathione levels in lab rats.[41][42]
Glutathione is a tightly regulated intracellular constituent, and is limited in its production by negative feedback inhibition of its own synthesis through the enzyme gamma-glutamylcysteine synthetase, thus greatly minimizing any possibility of overdosage. Glutathione augmentation using precursors of glutathione synthesis or intravenous glutathione is a strategy developed to address states of glutathione deficiency, high oxidative stress, immune deficiency, and xenobiotic overload in which glutathione plays a part in the detoxification of the xenobiotic in question (especially through the hepatic route). Glutathione deficiency states include, but are not limited to, HIV/AIDS, chemical and infectious hepatitis, myalgic encephalomyelitis chronic fatigue syndrome ME / CFS,[43][44][45] prostate and other cancers, cataracts, Alzheimer's disease, Parkinson's disease, chronic obstructive pulmonary disease, asthma, radiation poisoning, malnutritive states, arduous physical stress, and aging, and has been associated with suboptimal immune response. Many clinical pathologies are associated with oxidative stress and are elaborated upon in numerous medical references.[18][46][47]
Low glutathione is also strongly implicated in wasting and negative nitrogen balance,[48] as seen in cancer, AIDS, sepsis, trauma, burns and even athletic overtraining. Glutathione supplementation can oppose this process, and in AIDS, for example, result in improved survival rates.[49] However, studies in many of these conditions have not been able to differentiate between low glutathione as a result of acutely (as in septic patients) or chronically (as in HIV) increased oxidative stress, and increased pathology as a result of preexisting deficiencies.
Schizophrenia and bipolar disorder are associated with lowered glutathione. Accruing data suggest that oxidative stress may be a factor underlying the pathophysiology of bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). Glutathione (GSH) is the major free radical scavenger in the brain.[50] Diminished GSH levels elevate cellular vulnerability towards oxidative stress; characterized by accumulating reactive oxygen species. Replenishment of glutathione using N-acetyl cysteine has been shown to reduce symptoms of both disorders.[51]
[edit]Cancer
Preliminary results indicate glutathione changes the level of reactive oxygen species in isolated cells grown in a laboratory,[52][53] which may reduce cancer development.[54] [55] None of these tests were performed in humans.
However, once a cancer has already developed, by conferring resistance to a number of chemotherapeutic drugs, elevated levels of glutathione in tumour cells are able to protect cancerous cells in bone marrow, breast, colon, larynx, and lung cancers.[56]
[edit]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.[57]
[edit]Methods to determine glutathione
Reduced glutathione may be visualized using Ellman's reagent or bimane derivates such as monobromobimane. The monobromobimane method is more sensitive. In this procedure, cells are lysed and thiols extracted using a HCl buffer. The thiols are then reduced with dithiothreitol (DTT) and labelled by monobromobimane. Monobromobimane becomes fluorescent after binding to GSH. The thiols are then separated by HPLC and the fluorescence quantified with a fluorescence detector. Bimane may also be used to quantify glutathione in vivo. The quantification is done byconfocal laser scanning microscopy after application of the dye to living cells.[58] Another approach, which allows to measure the glutathione redox potential at a high spatial and temporal resolution in living cells is based on redox imaging using the redox-sensitive green fluorescent protein (roGFP)[59] or redox sensitive yellow fluorescent protein (rxYFP) [60]
July 30, 2001 -- Who wouldn't like to get their hands on a naturally occurring substance that acts as an antioxidant, an immune system booster, and a detoxifier? Something that can help your body repair damage caused bystress, pollution, radiation, infection, drugs, poor diet, aging, injury, trauma, and burns?
A handful of researchers are saying the antioxidant glutathione can do all that and maybe more. But can you believe such sweeping claims? What's the evidence to back them up? Here are what three experts have to say:
What Is Glutathione?
"Glutathione is a very interesting, very small molecule that's [produced by the body and] found in every cell," says Gustavo Bounous, MD, director of research and development at Immunotec and a retired professor of surgery at McGill University in Montreal, Canada. "It's the [body's] most important antioxidant because it's within the cell."
Antioxidants -- the most well known of which are vitamins C and E -- are important for good health because they neutralize free radicals, which can build up in cells and cause damage. Because glutathione exists within the cells, it is in a prime position to neutralize free radicals. It also has potentially widespread health benefits because it can be found in all types of cells, including the cells of the immune system, whose job is to fight disease.
Glutathione occurs naturally in many foods, and people who eat well probably have enough in their diets, says Dean Jones, PhD, professor of biochemistry and director of nutritional health sciences at Emory University in Atlanta. Those with diets high in fresh fruits and vegetables and freshly prepared meats are most likely just fine. On the other hand, those with poor diets may get too little.
What Does Glutathione Do?
The strong antioxidant effect of glutathione helps keep cells running smoothly. Bounous and another glutathione expert, Jeremy Appleton, ND, say it also helps the liver remove chemicals that are foreign to the body, such as drugs and pollutants.
Appleton is chairman of the department of nutrition at the National College of Naturopathic Medicine in Portland, Ore., and senior science editor for Healthnotes, a database on complementary and alternative medicineavailable at newspaper stands and health food stores.
Evidence for the important role that glutathione plays in health comes from studies in people who are severely ill.
"If you look in a hospital situation at people who have cancer, AIDS, or other very serious disease, almost invariably they are depleted in glutathione," says Appleton. "The reasons for this are not completely understood, but we do know that glutathione is extremely important for maintaining intracellular health."
How Should Glutathione Be Taken?
Glutathione is probably not well absorbed into the body when taken by mouth. One way to get around that is to take it by vein. A more practical solution is to take the precursors -- that is, the molecules the body needs to make glutathione -- rather than glutathione itself. While there is no solid proof this works, the consensus among experts is that that doing so will increase the amount of glutathione in the cells.
Bounous has developed a glutathione-enhancing product called Immunocal, which is made up of glutathione precursors, mainly the amino acid cysteine.
Who Does Glutathione Help?
Animal and laboratory studies have demonstrated that glutathione has the potential to fight almost any disease, particularly those associated with aging, since free radical damage is the cause of many of the diseases of old age.
"Theoretically, there are many very strong arguments in favor of a therapeutic use of glutathione," says Appleton. "But when people have actually tried to use glutathione as an oral supplement, nasal spray, or intravenously, the results have been more of a preliminary nature. The amount of research on glutathione as a supplement ... is very limited."
Nevertheless, people have tried glutathione for the treatment of a whole host of conditions, including cancer, high blood pressure, Parkinson's disease, Alzheimer's disease, cataracts, and male infertility.
The best studies have been conducted in cancer. One study involved women with ovarian cancer who were being treated with chemotherapy. Some of the women were also treated with intravenous glutathione. Those given the glutathione not only had fewer side effects from the chemotherapy but also had better overall survival rates.
Myriam Abalain of Montreal, Canada, is one of the many people who have taken Bounous's Immunocal to combat cancer. In 1996, at age 33, a routinePAP smear revealed she had precancerous cells on her cervix, which is one step away from having cervical cancer. The three specialists she visited all told her that a hysterectomy was her only option, but she hesitated to have such major, life-altering surgery.
Instead, she waited. For more than two years, her condition remained stable. Then a friend suggested she try Immunocal. After eight months of taking the supplement, her physician could no longer detect any precancerous cells. Does this mean Immunocal cured her? It's hard to say based on just one case like hers. It is possible her body went into remission naturally.
Even Bounous acknowledges there's no real proof his product cured her cancer, but he's working on conducting good clinical research, comparing individuals with cancer taking glutathione to those who are not.
What Are the Risks?
Overall, taking glutathione or its precursors in reasonable amounts appears to be quite safe, although it should be avoided in people with milk protein allergies and in those who have received an organ transplant. There is also some concern, however, about the safety of taking glutathione for the one condition for which there is the greatest evidence of its usefulness: cancer.
"People don't get concerned about these health-promoting [supplements] until they're in their 50s and 60s," says Emory's Dean Jones. At that point, they may already have the initial precancerous [cells]. Therefore, the supplements, just like they promote health in normal tissues, might promote health in the precancerous tissue."
Appleton recognizes this possibility but says "there's no evidence that supplementing with glutathione, even intravenously, is in any way going to make any cancer worse. In fact, the evidence we have suggests the opposite. It suggests that glutathione and other antioxidants, far from interfering with the activity of chemotherapy, appear to reduce side effects without decreasing efficacy and may, in fact, improve the efficacy of the chemotherapy in fighting cancer."
Bounous says his research has demonstrated that taking Immunocal actually lowers glutathione in cancer cells while increasing it in normal cells. As a result, the cancer cells are more vulnerable to chemotherapy, and the normal cells are protected.
The upshot? The experts disagree on who should take glutathione or its precursors. Bounous says everyone should take it in order to optimize overall health. Appleton would reserve it for people with cancer. Jones says it might only prove beneficial for those who eat poorly and are thus unlikely to be getting much glutathione or its precursors in their diet.
They all acknowledge that people with severe diseases known to be associated with low glutathione levels, such as AIDS, may well benefit from the supplement, although there is no proof to this effect.
For her part, Myriam Abalain is still taking Immunocal and feeling fine. "I'm doing pretty good now," she says. "I'm in better shape than ever!"
