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GSH is a simple molecule, composed of 3 common amino acids: glutamate, cysteine, and glycine, which are also found in protein throughout the body. The amino acids are connected in a unique way so that GSH can be made and broken down independently of the body’s protein. The structure controls the reactivity of a sulfur atom in the cysteine, which is critical for function. GSH reacts with toxic oxygen radicals to form GSH radicals and glutathione disulfide (GSSG), thereby protecting against oxidative damage to DNA and proteins. Living organisms depend on controlled reactions in which chemicals share and transfer electrons to maintain physical and chemical organization. Reactive chemicals with a high affinity for electrons destroy the organization and function because they interfere with the normal processes of sharing and donating electrons. The body is constantly exposed to damaging reactive chemicals, and GSH provides a general biological solution because the electron properties of the sulfur of GSH are ideally suited to protect against such chemicals.

In protection against an imbalance in electron transfer reactions, termed “oxidative stress,” GSH donates electrons to chemicals known as “oxidants.” Oxidants avidly accept electrons, and this disrupts normal electron flow. The electron-donating property of GSH protects against this; in the process, two molecules of GSH are converted to GSSG, an oxidized (disulfide) form. The balance of GSH and GSSG is quantified as the “GSH redox balance,” a measure of the status of the GSH system to protect against such oxidative challenges. In this expression, more reduced (more negative) “redox” values are generally healthy, while more oxidized (more positive) “redox” values are unhealthy. Values measured in blood are a reflection of tissue values because cells have transport systems for both GSH and GSSG. However, oxidation also occurs outside of cells, so under a normal, healthy state, the extracellular balance is oxidized relative to that in cells. Many diseased states have excessively oxidized extracellular GSH redox values.
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Where is GSH found in the body?
GSH is found in all tissues and body fluids. A healthy balance requires an unequal distribution of GSH and GSSG among these locations,6 similar to the need for sodium and potassium to differ between plasma and cells. In general, the concentrations of GSH within cells are much higher than outside of cells. Nonetheless, the amounts of GSH in the fluids surrounding cells are important because they provide a chemical-defense barrier to protect the cell surfaces.

The total amount of GSH in the body is about 15 grams, of which the cysteine component represents 5 grams. The organs principally responsible for detoxification (ie, the liver and kidneys), have the highest amounts, but the 15 grams are distributed among all major organ systems, including brain, heart, skeletal muscle, intestines, lungs, skin, and the immune system. The liver (6% of the body) has about 4 grams of GSH (25% of the body’s total), which is part of an important homeostatic mechanism. Liver GSH varies as a function of diet, time of day, and body needs. The cysteine content of liver GSH is similar to the RDA for sulfur amino acids (methionine plus cysteine), which is 1.4 g for a reference 70 kg individual. Thus, the GSH in the liver is equivalent to a 1-day reserve for the cysteine needed for the body’s protein synthesis.