Kinetics and mechanism of the glutathione-dependent reduction of dehydromethionine

Hypochlorous Acid Reacts with the N-Terminal Methionines of Proteins To Give Dehydromethionine, a Potential Biomarker for Neutrophil-Induced Oxidative Stress

“…DHM can be reduced by thiols; the half-life for the reaction of DHM (Chart 1, Z=OH) with cytosolic concentrations of glutathione is on the order of hours, although the rate in most physiologic fluids would be significantly less (19, 23). Accordingly, DHM (Chart 1, Z=OH) is potentially sufficiently long-lived in vivo to be detectable if it is formed.…”

“…For Met, it has been suggested that the sulfoxide (MetO) is the final product of oxidation by hypohalous acids (11–18). However, based upon previous studies of the I 3 − oxidation of Met, we suspected that dehydromethionine (DHM) might also be an intermediate (19–25). Indeed, we report herein that Met generally reacts with electrophilic halogenating agents to give high yields of DHM.…”

Natural Products Containing a Nitrogen–Sulfur Bond

“…Formation of dehydromethionine requires a sufficiently basic, free, amino group to achieve efficient nucleophilic attack on sulfur; therefore it is unlikely to occur with protonated and N-terminally modified methionine residues or methionine residues present within the polypeptide chain. ,, The role of formation of N-terminal dehydromethionine during inflammation is not known, but dehydromethione could be involved in some capacity in the global redox regulation of the cell. Despite the fact that cellular thiols such as glutathione are capable of reducing free dehydromethionine, its half-life in physiological conditions is measured in minutes to hours . This opens the possibility for dehydromethionine and similar sulfilimines to have a sufficient lifetime in vivo to allow their use in the cellular redox processes …”

“…Despite the fact that cellular thiols such as glutathione are capable of reducing free dehydromethionine, its half-life in physiological conditions is measured in minutes to hours. 388 This opens the possibility for dehydromethionine and similar sulfilimines to have a sufficient lifetime in vivo to allow their use in the cellular redox processes. 388 In vitro studies on model peptides suggest that both intra-and intermolecular sulfilimine bonds could form, in both their protonated and neutral forms, in the cellular environment, 347 although their true abundance in cells and overall stability over longer time scales (e.g., due to hydrolysis or to reactivity with cellular thiols) is sometimes doubted (Table 3).…”

“…388 This opens the possibility for dehydromethionine and similar sulfilimines to have a sufficient lifetime in vivo to allow their use in the cellular redox processes. 388 In vitro studies on model peptides suggest that both intra-and intermolecular sulfilimine bonds could form, in both their protonated and neutral forms, in the cellular environment, 347 although their true abundance in cells and overall stability over longer time scales (e.g., due to hydrolysis or to reactivity with cellular thiols) is sometimes doubted (Table 3). 389 It is also important to consider that halogen-activated formation of sulfilimines in proteins and peptides likely competes with the generation of numerous other N−S bond structures, such as sulfinamides or sulfonamides, that differ in their degree of sulfur oxidation and nitrogen protonation, 317,332 which might in the end further limit their overall impact on redox metabolism (Table 3).…”