Glutathion

Glutathione is a tripeptide composed of the amino acids glutamate, cysteine, and glycine. It is the most abundant intracellular thiol and serves as a major antioxidant and redox buffer in nearly all cells, helping to protect against oxidative stress and maintain cellular function.

Glutathione is synthesized in two ATP-dependent steps. The first step is catalyzed by γ-glutamylcysteine synthetase, forming γ-glutamylcysteine, and the second step by glutathione synthetase, adding glycine to produce glutathione (GSH). In cells, glutathione primarily exists in the reduced form (GSH); the oxidized form (glutathione disulfide, GSSG) accumulates when oxidative stress increases. The GSH/GSSG ratio is a key indicator of cellular redox status.

Functions of glutathione include detoxification and protection against oxidative damage. It participates in conjugation reactions with electrophilic compounds via glutathione S-transferases, aiding in the detoxification of xenobiotics and drugs. It also serves as a substrate for glutathione peroxidase, reducing hydrogen peroxide and lipid peroxides, with glutathione reductase regenerating GSH from GSSG using NADPH.

Distribution and roles extend beyond detoxification. Glutathione is most abundant in the liver but is present in virtually all tissues, including the cytosol, mitochondria, and nucleus. It contributes to maintaining thiol status, modulating signaling pathways, and supporting immune function. Levels can be influenced by aging, diet, illness, and environmental exposures.

Clinical and dietary aspects note that cysteine-rich diet or precursors (for example, N-acetylcysteine) can support glutathione synthesis. Glutathione status may be assessed in research and some clinical contexts, and severe depletion occurs in certain toxic states, such as acetaminophen overdose. Glutathione is not classified as a vitamin.