Evidence for the formation of Michael adducts from reactions of ( E, E)-muconaldehyde with glutathione and other thiols

Abstract

Glutathione induces the rapid isomerization of ( Z, Z)-muconaldehyde to ( E, E)-muconaldehyde via ( E, Z)-muconaldehyde, probably via reversible Michael addition of the thiol to one of the enal moieties of the muconaldehyde. Reactions of ( E, E)-muconaldehyde with glutathione (in the presence and absence of equine glutathione S-transferase), phenylmethanethiol, N-acetyl- l-cysteine, and N-acetyl- l-cysteine methyl ester were investigated using mass spectrometric techniques. In each case, evidence was obtained for the formation of Michael adducts, e.g., reaction between ( E, E)-muconaldehyde and glutathione gave 4-glutathionyl-hex-2-enedial and 3,4-bis-glutathionyl-hexanedial. These experiments suggest that ( Z, Z)-muconaldehyde, a putative metabolite of benzene, could lead to the long established urinary metabolite of benzene, ( E, E)-muconic acid, via glutathione-mediated isomerization to ( E, E)-muconaldehyde.