Glutathione is a peptide polymer composed of the amino acids glutamate, cysteine and glycine. A peptide is similar to a protein in that it is composed of amino acids linked by bonds, but peptides are shorter molecules. Although all cells in the human body can synthesize glutathione, the liver is the primary organ that maintains circulating levels of glutathione. Glutathione is involved in multiple functions of the body. A deficiency in its synthesis and/or export is instrumental in causing disease and is involved in mediating the aging process.
Synthesis
Two enzymes in the cytosol of cells are involved in the synthesis of glutathione. They are glutamylcysteine synthetase and glutathione synthetase. A review article in the "Journal of Nutrition" states that the synthesis of glutathione is primarily controlled by the activity of glutamylcysteine synthetase and the availability of the amino acid, cysteine. Cysteine is commonly found in high-protein foods. If protein nutrition is inadequate, glutathione levels decrease. A study published in the journal "Biological Chemistry" notes that glutathione levels are also affected by hormonal levels, pregnancy and exercise and they fluctuate between night and day and as a person ages.
Redox Reactions
Many biochemical reactions involve reduction and oxidation, also known as redox reactions. These types or reactions are essential for living organisms and are involved in many processes including making energy. Glutathione is a prominent player in redox reactions in the cell. It exists in two forms, oxidized and reduced in a cell. The reduced form, GSH participates in biochemical reactions by transferring electrons to other molecules, a process called reduction. All redox reactions include both a reducing step and an oxidizing step. In a reduction reaction, GSH is oxidized to glutathione disulfide, or GSSG. Cells also contain the enzyme, glutathione reductase, which rapidly replenishes GSH so that it can participate in other redox reactions.
Functions
Redox reactions are also involved in how an antioxidant protects cells from damage caused by reactive oxygen species. Reactive oxygen species are produced during normal metabolic events and they must be neutralized in order to prevent cellular damage. Glutathione is the primary cellular antioxidant and it neutralizes reactive oxygen species. It also detoxifies many foreign compounds also by redox reactions. Glutathione plays a role in several other cell functions, including DNA synthesis and repair, the expression of genes into proteins, nutrient metabolism, cellular communication and many actions of the immune system.
Glutathione Deficiency
The importance of glutathione actions in the human body is best illustrated in the severity of symptoms and low life expectancy in patients with rare genetic defects that decrease glutathione synthesis. The inborn errors of glutathione synthesis can result in destruction of the central nervous system, severe blood disorders, recurrent bacterial infections and compromised muscle control. Many diseases are influenced by chronic oxidative stress and are exacerbated by glutathione deficiency. A review article in the "Journal of Nutrition" states that glutathione deficiency contributes to the aging process and plays a role in causing diseases including malnutrition, Alzheimer's disease, Parkinson's disease, liver disease, cystic fibrosis, sickle cell anemia, AIDS, cancer, cardiovascular disease and diabetes.
Supplements
A study in the "European Journal of Clinical Pharmacology" reported that orally administered glutathione does not influence circulating levels of glutathione because it is broken down by digestion in the small intestine. Therefore, taking glutathione supplements will not lead to any therapeutic benefits. However, the review published in "Biological Chemistry" provided evidence that glutathione precursors, like N-acetylcysteine, can restore intracellular glutathione levels and have been shown to counteract disease processes and progression.
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