Figure 3.

Mechanism of lipid peroxidation. A free radical, for example associated with Aβ42 oligomers inserted into a lipid bilayer (Butterfield and Halliwell, 2019), attacks a lipid acyl chain-resident, labile allylic hydrogen atom to form the RH compound and a carbon-centered lipid free radical, L^.. Oxygen, which is paramagnetic with two unpaired electrons and has zero dipole moment, meaning it is highly soluble in the lipid bilayer, binds to the carbon-centered radical on the acyl chain to form the lipid peroxyl free radical, LOO^.. This free radical, in turn, abstracts another allylic hydrogen on a fatty acid chain of the lipid to from LOOH, the lipid hydroperoxide, and another lipid-resident, carbon-centered free radical, i.e., propagating the chain reaction. LOOH, through a series of chemical reactions, spontaneously will form HNE that can covalently bind to and change the conformation and function of membrane-resident proteins (Subramaniam et al., 1997; Sultana et al., 2013). In addition, HNE can diffuse from the lipid bilayer to covalently modify cytosolic proteins (Butterfield and Stadtman, 1997). Modified from Butterfield and Boyd-Kimball, 2019.