Glutathionem

Glutathionem, commonly called glutathione, is a small tripeptide that acts as a major cellular antioxidant. It is composed of the amino acids glutamate, cysteine, and glycine, and in biochemistry is described as γ-L-glutamyl-L-cysteinylglycine. In cells it exists mainly in two redox states: the reduced form (GSH) and the oxidized form (GSSG). The GSH/GSSG ratio reflects the cellular redox environment and can influence signaling pathways and enzyme activity.

It is synthesized in the cytosol by two ATP-dependent enzymes. First, gamma-glutamylcysteine synthetase (glutamate–cysteine ligase) combines glutamate and cysteine to form gamma-glutamylcysteine. Second, glutathione synthetase adds glycine to produce GSH. Cysteine availability is the rate-limiting step. Glutathione is especially abundant in the liver but is found in many tissues, in the cytosol and mitochondria and at least in small amounts in extracellular fluids.

Glutathionem serves as a key antioxidant by directly scavenging reactive oxygen and nitrogen species and as a substrate for glutathione peroxidases, which reduce hydrogen peroxide and lipid peroxides to water and lipid alcohols, generating GSSG. The enzyme glutathione reductase recycles GSSG back to GSH using NADPH. Glutathione participates in detoxification through glutathione S-transferases, which conjugate GSH to electrophilic xenobiotics and endogenous compounds. It also participates in redox signaling and protein S-glutathionylation. Clinically, low glutathione levels are associated with oxidative stress and several diseases; deficiencies can be due to genetic disorders or severe oxidative stress. Dietary intake provides amino acid precursors; supplementation exists, with formulations aimed at improving bioavailability, though efficacy varies.