By: evitamin.com

Glutathione is actually a tripeptide made up the amino acids gamma-glutamic acid, cysteine, and glycine. The primary biological function of glutathione is to act as a non-enzymatic reducing agent to help keep cysteine thiol side chains in a reduced state on the surface of proteins. Glutathione is also used to prevent oxidative stress in most cells and helps to trap free radicals that can damage DNA and RNA. There is a direct correlation with the speed of aging and the reduction of glutathione concentrations in intracellular fluids. As individuals grow older, glutathione levels drop, and the ability to detoxify free radicals decreases. (from: evitamins.com)

By: Encyclopedia Britannica.com

a tripeptide (i.e., compound composed of three amino acids), the chemical name of which is g-l-glutamyl-l-cysteinylglycine. Widely distributed in nature, it has been isolated from yeast, muscle, and liver. Glutathione has a role in the respiration of both mammalian and plant tissues and protects red blood cells against hydrogen peroxide, which is a toxic by-product of many...(from: Encyclopedia Britannica.com)

By: Zest for Life

Glutathione is actually a tri-peptide made up the amino acids gamma-glutamic acid, cysteine, and glycine and is also known as gamma-glutamylcysteinylglycine or GSH. It is as such not an amino acid, but because of its close relationship to amino acids, is dealt with here. It is found in the largest concentrations in the liver. (from: Zest for Life)

By: Wikipedia, the free encyclopedia

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 mmol 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. (from: Wikipedia, the free encyclopedia)

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). 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.

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.

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. All of the published clinical studies using bioactive whey proteins mentioned in the references above used a form of a bioactive whey protein and bonded cystine dietary supplement derived from lactose-free organic milk (whey protein) called Immunocal. This whey protein is clinically proven to increase glutathione levels within the lymphocytes of the immune system by 35.5% while increasing peak power and muscular performance by 13%.

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.

Glutathione Synthetase Deficiency

A rare disorder that prevents the production of glutathione. Glutathione helps prevent damage to cells by neutralizing harmful molecules generated during energy production. Glutathione also plays a role in processing medications and cancer-causing compounds (carcinogens), and building DNA, proteins, and other important cellular components.

Glutathione synthetase deficiency can be classified into three types: mild, moderate and severe. Mild glutathione synthetase deficiency usually results in the destruction of red blood cells (hemolytic anemia). Rarely, affected people also excrete large amounts of a compound called 5-oxoproline in their urine (5-oxoprolinuria). This compound builds up when glutathione is not processed correctly in cells.

Individuals with moderate glutathione synthetase deficiency may experience symptoms beginning shortly after birth including hemolytic anemia, 5-oxoprolinuria, and elevated acidity in the blood and tissues (metabolic acidosis). In addition to the features present in moderate glutathione synthetase deficiency, individuals affected by the severe form of this disorder may experience neurological symptoms. These problems may include seizures; a generalized slowing down of physical reactions, movements, and speech (psychomotor retardation); mental retardation; and a loss of coordination (ataxia). Some people with severe glutathione synthetase deficiency also develop recurrent bacterial infections.

Mutations in the GSS gene cause glutathione synthetase deficiency. The GSS gene provides instructions for making an enzyme called glutathione synthetase. This enzyme is involved in a process called the gamma-glutamyl cycle, which takes place in most of the body's cells. This cycle is necessary for producing a molecule called glutathione. Glutathione protects cells from damage caused by unstable oxygen-containing molecules, which are byproducts of energy production. Glutathione is called an antioxidant because of its role in protecting cells from the damaging effects of these unstable molecules which are byproducts of energy production.

Mutations in the GSS gene prevent cells from making adequate levels of glutathione, leading to the signs and symptoms of glutathione synthetase deficiency. This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.

Glutathione is required for

It is a powerful antioxidant and detoxifies the harmful compounds in the liver, where it is then excreted through the bile.

The liver also excretes glutathione directly into the bloodstream where it is used to help maintain the integrity of red blood cells, as well as protecting white blood cells.

Glutathione is also found in the lungs and intestinal tract where it assists in carbohydrate metabolism as well as breaking down oxidized fats.

It is also used to prevent oxidative stress in most cells and helps to trap free radicals that can damage DNA and RNA. GSH also plays major roles in drug metabolism, calcium metabolism, the gamma-glutamyl cycle, blood platelet and membrane functions.

Deficiency of glutathione

A deficiency of glutathione is first noticed in the nervous system with a lack of co-ordination, tremors, mental disorders, and body balance, all caused by lesions in the brain.

Dosage

The dosage listed is the Recommended Daily Allowance (RDA), but be aware that this dosage is the minimum that you require per day, to ward off serious deficiency of this particular nutrient. In the therapeutic use of this nutrient, the dosage is usually increased considerably, but the toxicity level must be kept in mind.

When more may be required

There is a direct correlation with the speed of aging and the reduction of glutathione concentrations in intracellular fluids. As individuals grow older, glutathione levels drop, and the ability to detoxify free radicals decreases.

Other interesting points

Supplements of glutathione are expensive, so it might be better to try and ingest more of this nutrient via your diet.

Food sources of glutathione

Foods rich in cysteine, glutamic acid and glycine should be selected when wishing to increase your dietary intake of this nutrient.

RDA - Recommended Dietary Allowance of nutritional elements

RDA, or known by its full name - Recommended Daily Allowance - is busy being revised and will be called the Dietary Reference Intake (DRI)

Although the abbreviation stands for the Recommended Dietary Allowance, although many refer to it as the Recommended Daily Allowance.

The RDA represents the establishment of a nutritional norm for planning and assessing dietary intake, and are the levels of intake of essential nutrients considered to be adequate to meet the known needs of practically all healthy people.

These figures were first published in 1943 and have been updated and expanded as data became available.

When introducing the new revision of the RDA in 1974, Dr. Alfred E. Harper, the then Chairman of the Committee on Dietary Allowances, Food and Nutrition Board said "...However requirements differ with age and body size; among individuals of the same body size owning to differences in genetic makeup; with the physiologic state of individuals - growth rate, pregnancy, lactation; and with sex. .."

With this in mind, herewith the tables as they stand at the moment:

Please be advised that these tables above must not be used to treat or diagnose - they are merely brought to you for information, in order to give you a better understanding on the dynamics involved, and the changing importance of vitamins and nutrition as well as their importance in maintaining optimum health.

RDA of amino acids

These figures below is an estimate of the required dietary allowance (RDA) of essential amino acids - that being those amino acids that can not be synthesized by the body.

Nitrogen balance and protein intake

When consuming an adequate amount of essential amino acids, the person will be classed as being in "nitrogen equilibrium", since nitrogen balance studies are conducted to determine the amounts of these essential amino acids required by various people, and this balance is reached when the intake of nitrogen from protein is approximately equal to the nitrogen lost in the feces and urine.

References

•1. Wikipedia, the free encyclopedia

•2. Zest For Life

•3. Encyclopedia Britannica.com

•4. evitamins.com