A schematic representation of the metabolic cascade for the non-enzymatic generation of isoprostanes. This is a proposed scheme in which four series of regioisomers of PGG2 are formed, before they are reduced to PGF2α isomers. As shown, isoprostanes can be formed from arachidonic acid in situ in phospholipids, from which they are presumably cleaved by phospholipases A2. PGG2 spontaneously rearranges to PGD2 and PGE2 thereby generating isoprostanes of the D and E series. The initial step in the formation of an isoprostane from arachidonic acid (I) is the generation of a lipid free radical by the abstraction of a hydrogen atom from one of the three methylene-interrupted carbon atoms, C7, C10, or C13, as shown here, by a free radical (FR•) which may be a hydroxyl radical (HO•), a superoxide radical (O2-•) or other free radical, and results in (II). Radical attack at C-10 is shown, abstraction at the other positions determines the relative proportion of the isomers formed. The lipid free radical is converted to a peroxy radical by reaction with molecular oxygen. The peroxy radical cyclizes in an intramolecular reaction that yields an endoperoxide (III). The free radical chain reaction will continue to propagate until quenched by an antioxidant.