What is Glutathione?

Glutathione (GSH) is a 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 at a concentration of approximately ~5 mM in animal cells. In effect, glutathione reduces any disulfide bonds formed within cytoplasmicproteins to cysteines by acting as an electron donor. Glutathione is found almost exclusively in its reduced form, since the enzyme that reverts it from its oxidized form (GSSG), glutathione reductase, is constitutively active and inducible upon oxidative stress. In fact, the ratio of reduced glutathione to oxidized glutathione within cells is often used scientifically as a measure of cellular toxicity.

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:

Glutamate cysteine ligase (GCL) is a heterodimeric enzyme composed of a catalytic (GCLC) and modulatory (GCLM) subunit. GCLC constitutes all the enzymatic activity, whereas GCLM increases the catalytic efficiency of GCLC. Mice lacking GCLC (i.e., all de novo GSH synthesis) die before birth. Mice lacking GCLM demonstrate no outward phenotype, but exhibit marked decrease in GSH and increased sensitivity to toxic insults.

While all cells in the human body are capable of synthesizing glutathione, liver glutathione synthesis has been shown to be essential. Following birth, mice with genetically-induced loss of GCLC (i.e., GSH synthesis) only in the liver die within 1 month of birth.

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