The formation of 4-HNE from arachidonic acid by lipid peroxidation, chain break, and hydroxylation. In malaria, it was shown that the heme core of hemozoin (HZ, malaria pigment) could catalyze the lipoperoxidation of PUFAs. Resulting hydroperoxides are chemically unstable: they (i) are reduced to the hydroxy-fatty acid such as hydroxyeicosatetraenoic acid (HETE) from arachidonic (note, HETEs are bioactive PPAR-γ (peroxisome proliferator-activated receptor gamma) ligands) or (ii) are decomposed to 4-HNE. C1 and C3 are 4-HNE reactive sites. Biologically relevant properties of 4-HNE are listed in blue.