Glutathione

Glutathione (GSH) is a tripeptide composed of glutamate, cysteine, and glycine, linked by an unusual gamma peptide bond between the glutamate side chain carboxyl and cysteine. It is the most abundant intracellular thiol and the principal antioxidant in cells, present in millimolar concentrations in most tissues with particularly high levels in the liver.

Glutathione plays critical roles in detoxification, immune function, protein synthesis, and maintaining the reduced state of other antioxidants. Its thiol group (-SH) on cysteine is the active site for its antioxidant and conjugation functions.

Glutathione functions through several interconnected mechanisms:

Antioxidant Defense GSH directly neutralizes reactive oxygen species (ROS) and reactive nitrogen species. It reduces hydrogen peroxide via glutathione peroxidase and regenerates oxidized vitamins C and E back to their active forms.

Detoxification Through glutathione S-transferases (GSTs), GSH conjugates with xenobiotics, drugs, and toxins, making them more water-soluble for excretion. This is a major Phase II detoxification pathway in the liver.

Thiol-Disulfide Exchange GSH maintains proteins in their reduced state by providing reducing equivalents. The GSH/GSSG (reduced/oxidized) ratio is a key indicator of cellular redox status and ranges from 100:1 to 10:1 in healthy cells.

Immune Function GSH is essential for lymphocyte proliferation and function. It modulates the inflammatory response and is required for proper immune cell activity.

Protein Synthesis GSH is required for DNA synthesis and protein synthesis, acting as a substrate for various biosynthetic reactions.