gammaglutamylcysteine

Gamma-glutamylcysteine is a dipeptide consisting of a gamma-glutamyl moiety linked to cysteine. It is a key intermediate in the biosynthesis of glutathione, the cell’s major antioxidant.

The dipeptide is formed by the enzyme gamma-glutamylcysteine synthetase (also called glutamate–cysteine ligase), which catalyzes an ATP-dependent condensation of glutamate and cysteine. This step is the rate-limiting stage in glutathione synthesis. The next step adds glycine to gamma-glutamylcysteine via glutathione synthetase to form glutathione (GSH).

Gamma-glutamylcysteine is primarily produced in the cytosol of cells. It serves as the immediate precursor to glutathione and participates in the gamma-glutamyl cycle, a pathway involved in amino acid transport and glutathione turnover. Its cellular levels generally appear lower than those of glutathione.

Regulation of gamma-glutamylcysteine levels reflects the activity of gamma-glutamylcysteine synthetase and the cell’s demand for GSH. Oxidative stress or toxins can upregulate the synthesis pathway to boost glutathione production. Deficiencies in glutathione synthesis lead to increased susceptibility to oxidative damage, and precursors such as N-acetylcysteine are sometimes used to support cysteine supply for GSH production.

In research contexts, gamma-glutamylcysteine is measured to assess a cell’s capacity for glutathione synthesis and redox status. Analytical methods include chromatography in tissue or fluid samples.