Figure 1.

Overview of Nonenzymatic Lipid Peroxidation and Tocopherol Scavenging.

(A) In step 1, free radicals attack the double bonds of PUFA acyl chains, creating a lipid radical that readily reacts with an oxygen molecule, forming a lipid peroxyl radical. In step 2, in the absence of tocopherols or other lipid-soluble antioxidants, such as DMPBQ in vte1, the lipid peroxyl radical can attack neighboring PUFAs, propagating a chain reaction. In step 3, tocopherols can scavenge lipid peroxyl radicals by donation of a hydrogen atom, thereby reducing the radical and blocking further propagation. In step 4, a linolenic acid (18:3) peroxyl radical can also react internally, forming a cyclic peroxyl radical, which spontaneously reacts with a second oxygen molecule and is subsequently reduced to phytoprostane G₁ (PPG₁). In step 5, PPG₁ either spontaneously decays, forming MDA and other alkanes and alkenes, or forms other phytoprostanes. In step 6, lipid peroxides are converted to their corresponding hydroxy fatty acid either enzymatically or spontaneously.

(B) PPG₁ spontaneously rearranges, forming PPD₁, PPE₁, and PPF₁. PPD₁ and PPE₁ in turn rearrange to form dPPJ₁ and PPA₁, respectively. PPA₁ can further rearrange to form PPB₁. There are multiple stereoisomers and enantiomers for each phytoprostane family (e.g., PPE₁, PPF₁) that are not shown. Note the structural similarity between dPPJ₁ and the enzymatically derived oxylipins jasmonic acid (JA) and its precursor 12-oxophytodienoic acid (OPDA).