Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation

Glutathione is a tripeptide consisting of three amino acids – glutamic acid, cysteine, and glycine.

It plays a pivotal role in detoxification via glutathione conjugation, a phase II biotransformation reaction.

This process entails the conjugation of glutathione with xenobiotics via nucleophilic substitution or addition reactions.

Unlike other conjugation reactions, glutathione conjugation does not require coenzyme or substrate activation due to glutathione's high nucleophilicity.

The core reaction occurs when glutathione's thiol group attacks the electrophilic center of the xenobiotic, forming a glutathione conjugate.

This reaction is catalyzed by enzymes known as glutathione S-transferases.

Glutathione conjugates are further metabolized, losing glutamine and glycine to form mercapturic acids. These acids are more stable and highly water-soluble, so they are easily excreted.

Glutathione conjugation helps effectively detoxify xenobiotics. For instance, reactive intermediates of drugs like acetaminophen, are conjugated to glutathione to prevent hepatotoxicity.