Glutathione conjugation

A phase II conjugation reaction catalysed by glutathione transferase. Glutathione is a tripeptide (Glu-Cys-Gly) with the middle cysteine containing a side chain that terminates in a thiol (SH) group. Through this thiol group, the tripeptide can be attached to an electrophilic species (usually a reactive drug metabolite capable of causing significant damage to cell membranes and DNA), and the resulting bond rearrangement results in detoxification of the electrophilic species.

The body has a limited supply of glutathione, so when exposed to relatively large amounts of toxic electrophiles (such as occurs after taking a dose of acetaminophen that exceeds the recommended dose), glutathione can become depleted, and protection against damage is lost. This is why an overdose of acetaminophen, for example, causes irreversible liver damage. It is possible to administer other thiol compounds such as methionine or N-acetylcysteine to patients; these can combine directly (non-enzymatically) with electrophiles, helping to prevent cellular damage. Some acetaminophen preparations contain methionine so that if an overdose is ingested, the patient has also ingested an excess of protective methionine.