7-S-Glutathionyltryptophan-4,5-dione: Formation from 5-Hydroxytryptophan and Reactions with Glutathione

The electrochemically driven oxidation of 5-hydroxytryptophan (5-HTPP) in the presence of free glutathione (GSH) yields 4-S-glutathionyl-5-hydroxytryptophan (5) and 7-S-glutathionyl-tryptophan-4,5-dione (7). The latter glutathionyl conjugate is formed both by nucleophilic addition of GSH to tryptophan-4,5-dione (4), a normal product of the oxidation of 5-HTPP, and by oxidation of5in a reaction where the glutathionyl residue migrates from the C(4)- to the C(7)-position. In the presence of free GSH7reacts to give the 3,7- and 6,7-bi-S-glutathionyl conjugates of4and, as a result of intramolecular cyclization reactions, a number of glutathionyl conjugates of an unusual tricyclic pyrroloquinoline. It is speculated that one or more of these products might represent aberrant oxidative metabolites that have been detected in the cerebrospinal fluid of patients with Alzheimerʹs Disease.