L-Glutathione: How GSH and GSSG Detoxify the Liver and Improve Health

The tripeptide L-glutathione is synthesized in the body from L. glutamic acid, L-cysteine and glycine, a reaction that can occur in any cell of the body although it is essential that it also occurs in the liver. Should glutathione concentrations drop, they can be increased by supplementing with cysteine or any other of the three amino acids that are used in the biosynthesis of this important if substance

The tripeptide exists in two forms: the reduced form (GSH) which contains a sulfhydryl (SH) functional group attached to the cysteinyl part of the molecule, and the oxidized form glutathione disulfide (GSSG). As electrons are lost from the reduced form, two molecules combine to create a dimer formed by a disulfide bridge, the process which can be reversed through reduction of the GSSG. Such electrons are lost during its reaction with free radicals, in which the free radicals are neutralized by the donation of an electron from the oxidized version of glutathione.

The definition of a free radical is a molecule that is lacking one electron from an electronic pair. Its prime purpose is then to steal an electron from the nearest molecule to it. In doing so, it can not only destroy that molecule, but also destroy body cells and lead, not only to premature aging, but also to some potentially fatal conditions.

It is an unusual peptide in that it involves a link between the cysteine amino grouping and the carboxyl functional group of the glutamic acid. It is a powerful antioxidant, acting as an effective free radical scavenger and protecting the body cells from the effects of free radical oxidation. However, it is on its detoxification effect in the liver that we shall focus here prior to discussing some other uses to which the body puts glutathione in its two manifestations.

Much of the detoxification is connected with the thiol group in the molecule. Take mercury for example. The thiol grouping forms a strong Hg-sulfydryl chemical bond within the liver, in the form of a glutathione-mercury chelate. In this form mercury is unable to exert any toxic effect on the body and can be excreted in the normal manner. The same reactive pathway is followed by other heavy metals that can bond to thiol groupings. In this way L-glutathione can protect the liver from the effects of a number of toxic heavy metals such as cadmium and chromium.

This is an important property of the amino acid, particularly in industrial and urban environments where the population is more prone to exposure to heavy metals than their rural counterparts. However, the end result on the glutathione is that it is removed from the body, and, particularly with city dwellers, a supplement may be required to maintain a healthy concentration of this amino acid in the body and in particular in the liver. Therefore, although L-glutathione is not considered an essential amino acid, in that it is biosynthesized within the body, a supplement is sometimes required, particularly by those who live in large cities.

It is important to consider the form in which the glutathione supplement is administered. This is because of the presence of gamma-glutamyltranspeptidase within the digestive system. This enzyme appears to destroy L-glutathione before it can be absorbed in the intestine so normal oral forms of supplementation are likely to be ineffective. Possible forms of effective administration include buccal (between the cheek and teeth) and hypodermically.

An alternative means of supplementation is to take substances such as selenium, methionine, alpha-lipoic acid, vitamin C and glutamine that stimulate the biosynthesis of glutathione. Also, since the substance utilizes the raw materials of L-cysteine, glutamic acid and glycine in its intracellular production, supplementation with these amino acids should also help to produce L-glutathione.

That said, let's return to its antioxidant properties and its effect on the liver that contains the largest stocks of glutathione in the body. It is generally regarded as the most important antioxidant in the body. It protects cellular cytoplasm from oxidation by reducing disulfide groups and maintaining a highly reducing environment within the cytoplasm. It reacts with hydrogen peroxide and other oxidative agents, and is converted to the oxidized form GSSG. It is then reduced back to GSH through the combination of the reducing agent and an enzyme. The reducing agent is nicotinamide adenine dinucleotide phosphate (NADPH), the enzyme being glutathione reductase.

The implications that this strong reducing effect has on the liver are significant. Reduced GSH L-glutathione levels have been found in patients suffering from HIV, hepatitis C and other liver diseases. Supplementation with GSH has been found to restore normal levels of glutathione to the liver, and it has been demonstrated that the treatment has improved such conditions significantly.

Atherosclerosis is a condition of the arteries caused by the deposition of plaques formed from oxidized low-density lipoproteins, otherwise known as bad cholesterol. The strong antioxidant effect of GSH prevents this from LDLs from being oxidized and deposited on the arterial wall. There are other results of glutathione supplementation that indicate the effectiveness of antioxidants in the treatment of serious liver conditions, and there are no doubts that combating the effects of free radicals and oxidizing agents within the liver has a positive effect on many potentially serious liver diseases.

Many of these are exacerbated by the generation of free radicals by relatively modern pollution sources such as pesticides, petrol and diesel emissions, tobacco fumes and various other chemical emissions. A strong antioxidant such as L-glutathione cannot be anything other than an effective means of reducing the biological effect of these oxidants. It protects not only the liver but also the lungs and cardiovascular system.

For all these reasons a supplement consisting of L-glutathione or its constituent parts, glutamic acid, cysteine and glycine, provide significant protection against the stresses and strains of modern living. Increased pollution levels and heightened oxidative stress levels within the body are playing havoc with our body defenses, and GSH is an important one of them that can easily be enhanced by supplementation. There are no known reactions to L-glutathione supplementation, but pregnant women and babies should receive expert medical advice prior to taking it.