Figure 2. Formation of 4-hydroxy-2-trans-nonenal (HNE) from arachidonic acid.
The catalytic conversion of the Aβ(1-42) Met-35 S-atom to the sulfuranyl radical cation leads to the abstraction of a labile, allylic H-atom from unsaturated fatty acyl chains within the bilayer. In particular, arachidonic acid is a common fatty acid within the bilayer that is readily oxidized to produce one of the highly reactive lipid peroxidation products, HNE. Reactive oxygen species (ROS) other than Aβ(1-42) can also oxidize arachidonic acid to form a reactive hydroperoxide intermediate that is quickly converted to a peroxyl radical by Fe2+ (Fenton chemistry). The highly reactive peroxyl radical causes a molecular rearrangement which cyclizes the radical, arachidonic acid intermediate. Further oxidation and Fenton chemistry results in the β-scission of the cyclized intermediate, causing eventual formation of HNE.