Multi-defense pathways against electrophiles through adduct formation by low molecular weight substances with sulfur...

There is a variety of electrophiles in the environment. In addition, there are precursor chemicals that undergo metabolic activation by enzymes and conversion to electrophiles in the body. Although electrophiles covalently bind to protein nucleophiles, they also form adducts associated with adaptive or toxic responses. Low molecular weight compounds containing sulfur are capable of blocking such adduct formation by capturing the electrophiles. In this review, we present our findings on the capture and inactivation of electrophiles by: (i) intracellular glutathione, (ii) reactive sulfur species, and (iii) extracellular cysteine (formed during the production of sulfur adducts). These actions not only substantially suppress electrophilic activity but also regulate protein adduct formation.