The enzymes responsible for the regulation of cellular lipid electrophilesefficiently control the intracellular levels of HNE under basal conditions.However, during oxidative stress the threshold of the enzymes isovercome by the increased production of lipid electrophiles, thus exposingcellular acromolecules to the deleterious effects of HNE. Since GSHconjugation is the primary and major step in the detoxification of HNE,it is not surprising that depletion of GSH exposes cellularmacromolecules
to lipid electrophiles [35,36]. The reduction in cellular GSH levels resultsin a concomitant increase in circulating HNE [37]. HNE can be catabolizedto acetyl-CoA, propionyl-CoA, and formate through β-oxidation [38]. Theincrease in HNE and its catabolic intermediates can result in increased cytotoxicity.
Therefore, during oxidative stress, the level of reactive lipidelectrophiles becomes so high that the cell is unable to compensatewith detoxification mechanisms and, as a result, deleterious effects areobserved.