[21].HNE is able to spontaneouslyform Michael adducts with GSH to form GSH conjugates. Alternatively,the conjugation of GSH to the α,β-unsaturated carbonyl can be catalyzedby glutathione-S-transferases (GSTs), including hGSTA4-4 and hGST5.8,in a reaction that proceeds several hundred times faster than the spontaneousreaction [29–31]. The resulting product, GSH-HNE, is water solubleand able to be pumped from cells by glutathione conjugate export pumps
and, ultimately, excreted from the body in urineAdditionally, thealdehyde moiety of HNE can either be reduced into alcohol or oxidizedinto acid in reactions catalyzed by alcohol dehydrogenase, aldo–ketoreductasesand aldehyde dehydrogenase, respectively. Specifically, alcoholdehydrogenase and aldo–ketoreductases (AKRs) catalyze the reductionof 4-hydroxyalkenals and their GSH-conjugates to 1,4-ihydroxy-2-nonene (DHN) or GSH-DHN,which are less toxic and able to be efficientlycleared from the cell