What is reduced glutathione?

Reduced glutathione (GSH) is a crucial antioxidant that supports healthy liver function. It is found in high concentrations in cellular systems and plays a crucial role in detoxification of various substances. GSH is a tripeptide composed of L-glutamine, L-cysteine, and glycine. A deficiency of glutathione would result in a cell being at risk for oxidative damage. 

In the reduced state, GSH is a major tissue antioxidant that neutralizes reactive oxygen species. As a result of donating an electron, GSH itself becomes reactive and will readily react with other reactive GSH molecules to form GSSG. Additionally, reduced GSH provides reducing equivalents for the glutathione peroxidase (GPx) catalyzed reduction of lipid hydroperoxides to their corresponding alcohols and hydrogen peroxide to water. In the GPx catalyzed reaction, the formation of a disulfide bond between two GSH molecules forms GSSG. The enzyme glutathione reductase (GR) recycles GSSG to GSH while simultaneously oxidizing β-nicotinamide adenine dinucleotide phosphate (β-NADPH2).

Monitoring reduced GSH and its ratio with oxidized GSSG may be used to evaluate the redox and detoxification status of cells and tissues in relation to the protective role of glutathione against oxidative and free-radical-mediated cell injury. Under normal conditions, the GSH redox couple in mammalian cells typically ranges in concentration from 1 - 10 nM, with resting cells having molar GSH:GSSG ratios exceeding 100:1. When cells are exposed to increased levels of oxidative stress, GSSG accumulates and the ratio of GSH/GSSG decreases to ratios as low as 10:1 and even 1:1. As such, monitoring GSH/GSSG levels in biological samples has become a useful tool in evaluating oxidative stress of cells and tissues, and cell injuries caused by free radicals.