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-h ydroxytryptophan (5) and 7S-glutathionyltryptophan-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 of 5 in a reaction where the glutathionyl residue migrates from the C(4)- to the C(7)-position. In the presence of free GSH 7 reacts to give the 3,7- and 6,7-bi-S-glutathionyl conjug ates of 4 and, as a result of intramolecular cyclization reactions, a number of glutathionyl conjugates of an unusual tricyclic pyrroloquino line. It is speculated that one or more of these products might repres ent aberrant oxidative metabolites that have been detected in the cere brospinal fluid of patients with Alzheimer's Disease. (C) 1996 Academi c Press, Inc.