Figure 2.

(A) Mechanism of lipid peroxidation. Arachidonic acid structure showing labile allylic H-atoms that are subject to free radical-mediated abstraction (Rxn 1) leading to carbon-centered free radical on the lipid-resident arachidonic acid carbon backbone. Paramagnetic molecular oxygen, in a radical–radical recombination reaction (Rxn 2), produces the lipid-bound peroxyl free radical. This latter free radical abstracts another labile allylic H-atom (Rxn 3) to form the lipid hydroperoxide and another carbon-centered free radical. Then, this latter radical takes part in Rxn 2 again, i.e., a chain reaction, that will continue as long as there are molecular oxygen and allylic H-atoms present. The lipid hydroperoxide is decomposed into reactive aldehydes, including the highly reactive 4-hydroxynonenal (HNE). See text for additional details. (B). Formation of 3-nitrotyrosine. Nitric oxide (NO), a free radical produced by nitric oxide synthase from arginine, reacts with superoxide free radical anion (see Figure 1) by radical–radical recombination to form peroxynitrite, ONOO⁻. The actual next reaction shown is more complicated than depicted, but in essence, the protonation of peroxynitrite forms peroxynitrous acid that decomposes into the free radical nitrogen dioxide (NO₂) and hydroxyl free radical. Tyrosine, attacked by a free radical R^. to remove the H-atom of the phenolic OH group, leaves an unpaired electron on the O-atom that delocalizes to the 3-position of tyrosine with the H-atom removed from the 3-position, reforming the OH functional group on Tyr. NO₂ reacts with the delocalized unpaired electron on the 3-position of tyrosine residues in a radical–radical recombination reaction to form 3-nitrotyrosine (3-NT), which is a major marker of nitrosative stress. See the text for further details.