Glutathione

Glutathione (GSH) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides, and heavy metals. It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side chain and cysteine. The carboxyl group of the cysteine residue is attached by normal peptide linkage to glycine. Glutathione biosynthesis involves two adenosine triphosphate-dependent steps: While all animal cells are capable of synthesizing glutathione, glutathione synthesis in the liver has been shown to be essential. GCLC knockout mice die within a month of birth due to the absence of hepatic GSH synthesis. The unusual gamma amide linkage in glutathione protects it from hydrolysis by peptidases. Glutathione is the most abundant thiol is animal cells, ranging from 0.5 to 10 mM. It is present both in the cytosol and the organelles. Humans synthesize glutathione, but a few eukaryotes do not, including Leguminosae, Entamoeba, and Giardia. The only archaea that make glutathione are halobacteria. Some bacteria, such as cyanobacteria and proteobacteria, can biosynthesize glutathione. Glutathione exists in reduced (GSH) and oxidized (GSSG) states. The ratio of reduced glutathione to oxidized glutathione within cells is a measure of cellular oxidative stress. In healthy cells and tissue, more than 90% of the total glutathione pool is in the reduced form (GSH), with the remainder in the disulfide form (GSSG). An increased GSSG-to-GSH ratio is indicative of oxidative stress. In the reduced state, the thiol group of cysteinyl residue is a source of one reducing equivalent. Glutathione disulfide (GSSG) is thereby generated. The oxidized state is converted to the reduced state by NADPH. This conversion is catalyzed by glutathione reductase: