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Glutathione (GSH), due to the ability to capture the reactive electrophiles of exo- and endogenous origin, is expected to prevent cross-linking induced by these compounds. However, it may instead become cross-linked itself. We subjected glutathione to reactions with model α,β-unsaturated carbonyl systems resulting from the interactions of adenosine with bifunctional aldehyde products of lipid peroxidation, and identified a range of adducts and cross-linked products. We found that the S-conjugated adducts, initially formed in the typical for GSH Michael addition to α,β-unsaturated carbonyl system, unexpectedly undergo gradual degradation giving rise to the final N-conjugated products, in which formation of the peptide amino group was involved instead of the sulfhydryl functionality. This finding shows that the role of the GSH amino group in the non-enzymatic detoxification is underestimated and that reactions between cellular α,β-unsaturated carbonyl compounds, and GSH may be more complex than are presently perceived.