GLUTATHIONE PEROXIDASE:

Glutathione peroxidase belongs to the family of selenoproteins and plays an important role in the defense mechanisms of mammals, birds and fish against oxidative damage by catalyzing the reduction of a variety of hydroperoxides, using glutathione as the reducing substrate.

Four distinct species of glutathione peroxidase have been identified in mammals to date, the classical cellular enzyme, the phospholipid hydroperoxide metabolizing enzyme, the gastroinestinal tract enzyme and the extracellular plasma enzyme. Their primary structures are poorly related. It has been shown that they are encoded by different genes and have different enzymatic properties. Recently, we determined the crystal structure of the human plasma glutathione peroxidase at 2.9. A number of structural differences were observed between the human plasma enzyme and the bovine cellular enzyme whose structure had been solved previously. Structural comparison indicated that all the residues which were previously suggested to be involved in glutathione binding have been mutated or deleted in the plasma enzyme. The observed structural differences between the two enzymes suggest differences in substrate binding and specificity.

GLUTATHIONE

Glutathione is a key substance found in every cell in our body, and may be thought of as a "naturally occurring universal drug" – and one without adverse side effects! It is the cell’s most important antioxidant, neutralizing "free radicals" that would otherwise damage or destroy the cells. The body produces free radicals during metabolism. Under any form of stress, such as chemical toxicity or bacterial infections, the body generates many more free radicals. If glutathione is in short supply, these free radicals can overwhelm the cell. Exposure to radiation from sunlight or other sources also results in increasing highly reactive free radicals that likewise our bodies need to neutralize.

Glutathione is also the main detoxifying agent in the body. It converts damaging chemical substances (toxins) into harmless products that the body eliminates. Such chemicals include cancer-producing substances, heavy metals, herbicides, pesticides, smoke and other pollutants. Thus, glutathione provides important protection against many environmental hazards. The liver is particularly rich in glutathione for this purpose.

The immune system is our main defense against infection. Once again, glutathione plays a vital role, enabling the immune system to function optimally, which it cannot do when glutathione is deficient. For example, the cells of the immune system (lymphocytes) cannot multiply as much, cannot produce as many antibodies, and cannot kill unwanted cells like cancer cells or those infected with a virus. Glutathione deficiency also adversely affects other systems and organs such as the lungs, the nervous system, and the intestinal tract.

It is on record that there are many medical disorders associated with glutathione deficiency. These include AIDS and cancer wasting, some intestinal disorders, lung diseases, over-trained athletes syndrome and trauma. Furthermore, as we age, glutathione levels decrease which no doubt explains, in part, an older person’s lowered resistance to disease.

Glutathione is a very small protein made inside the cells from three amino acids obtained ultimately from our food or supplementation. One of these amino acids, cysteine, gives the glutathione its antioxidant and detoxifying properties. This amino acid is relatively rare in foodstuffs and this can lead to glutathione deficiency, even in healthy people. For example, one study demonstrated that, by feeding a cysteine enriched food product, glutathione values increased by 35.5% in the lymphocytes of normal young adults. (see reference below)

 

What is Glutathione

Glutathione is a small molecule made up of three amino acids, which exists in almost every cell of the body. However, Glutathione, must be generated within the cell from its precursors before it can work effectively in the body.

The presence of glutathione is required to maintain the normal function of the immune system. It is known to play a critical role in the multiplication of lymphocytes (the cells that mediate specific immunity) which occurs in the development of an effective immune response.

Furthermore, the cells of the immune system produce many oxiradicals as a result of their normal functioning, resulting in a need for higher concentrations of antioxidants than most cells. Glutathione plays a crucial role in fulfilling this requirement.

Glutathione as a Detoxicant

Supplemental detoxicants become necessary as our environment becomes increasingly polluted. Our food and water sources are contaminated with chemicals. One of our main defenses against pollutants is glutathione, which is present in the liver in high concentrations. Glutathione acts as a detoxifying agent by combining with undesirable substances and ridding the body of them through urine and bile.

To Get a Little More Technical About Glutathione

"Glutathione is a ubiquitous tripeptide molecule, consisting of three amino acids joined together. These are cysteine, glutamic acid and glycine - three of the twenty two amino acids which comprise the building blocks of all known proteins. In general, the amino-end of one amino acid combines with the acid-end of another to form a peptide bond with the elimination of water. Chains of amino acids are called proteins. The sequence of amino acids and the arrangement in space of each peptide bond defines some specific structural features of all proteins and olegopeptides (few amino acids in sequence) that relate to their function."

"Glutathione is only synthesized inside cells, in a series of steps catalysed by specific enzymes."

Glutathione is only synthesized inside the cell

"Many attempts have been made to enhance glutathione but beside the use of whey protein concentrate, all other approaches have proved futile for a number of reasons."

Source Dr. Allan Somersall PhD, M.D.

Glutathione (Psychoneurobiology)

"Free radicals and oxyradicals have been recognized by psychoneurobiologist as playing an important role in the development and progression of many of these disorders. The brain is particularly susceptible to free radical attack because it generates more oxidative-by-products per gram of tissue than any other organ. The brain's main antioxidant is glutathione- it's importance cannot be overstated."

"Oxidative stress and glutathione are important factors in such various disorders as brain injury, neurodegenerative disease, schizophrenia, Down syndrome and other pathologies."

Disorders of the brain and nervous system that are linked to oxidative stress

"Many neurological and psychiatric disease processes are characterized by high levels of oxidative stress and free radical formation, as well as abnormalities in glutathione metabolism and antioxidant defenses."

Source Dr. Gutman M.D. Glutathione GSH

Dr. Perlmutter: "Eighty to ninety percent improve dramatically. It's felt that the mechanism that allows it to work is in increasing the sensitivity to certain receptors to dopamine. Glutathione doesn't raise dopamine levels, but it allows the dopamine in the brain to be more effective. That's not a new idea in medicine. Diabetic drugs work not by increasing insulin, but by increasing the receptors to insulin. Glutathione not only increases sensitivity to dopamine, but also to serotonin, which may explain why many of our depressed PD patients have a remarkable improvement."

Increasing glutathione in the body has been proven to be essential in the treatment of disease. Antidepressants and other medications deplete the body and brain of glutathione. 

Functions of Glutathione

Enhancing the Immune System - Your bodies immune activity, involving unimpeded multiplication of lymphocytes and antibody production, requires maintenance of normal levels of glutathione inside the lymphocytes.

Antioxidant and Free Radical Scavenger - Glutathione plays a central protective role against the damaging effects of bacteria, viruses, pollutants and free radicals.

Regulator of Other Antioxidants - Without glutathione, other important antioxidants such as vitamins C and E cannot do their job adequately to protect your body against disease.

A Detoxifying Agent - Another major function of glutathione is in the detoxification of foreign chemical compounds such as carcinogens and harmful metabolites.

How Can Glutathione (GSH) Be Administered

Oral (by mouth) - GSH is digested or broken down into its amino acid constituents and by themselves, those have not effect.

Intravenous (by needle) - GSH has a very short half-life in the circulation.

Intratracheal (by aerosol inhalation) - GSH would not only affect the respiratory linings, briefly.

Intraperitoneal (by abdominal wall) - GSH plasma levels rise but there is no increase in the tissues such as the liver, lung or lymphocytes.

There is significant evidence that the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Friedreich's ataxia and amyotrophic lateral sclerosis, may involve the generation of reactive oxygen species and mitochondrial dysfunction. Glutathione is an important intracellular antioxidant that protects against a variety of different antioxidant species. An important role for glutathione was proposed for the pathogenesis of Parkinson's disease, because a decrease in total glutathione concentrations in the substantia nigra has been observed in preclinical stages, at a time at which other biochemical changes are not yet detectable.

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