Lipid peroxidation is a well-known natural phenomenon associated with both health and disease, that originates on Poly-Unsaturated Fatty Acid chains.
PUFA possess methylene groups that reside between two double bonds known as bisallylic groups (-CH=CH-CH2-CH=CH-) that have hydrogen with weakened bond energies due to the attraction of their electrons to the double bonds on either side. Since monounsaturated fatty acids possess allylic rather than bisallylic methylene groups, their carbon–hydrogen bond energies are stronger and less prone to cleavage whereas the methylene groups of saturated fats, with a total lack of double bonds have even stronger carbon– hydrogen bond energies and are highly resistant to peroxidation.
The rates of peroxidation of PUFA occur in proportion to the total number of bisallylic groups available and this has provides a relative scale of peroxidation known as the peroxidation index.
Recently, Else PL and Kraffe E (Biochimica and Biophysica Acta, 2015) demonstrated that peroxidation of PUFA with more than one bisallylic group is primarily an intramolecular process rather than an intermolecular process. The implications of intramolecular peroxidation of these highly polyunsaturated fats in membranes are that they are likely to produce localized high concentrations of peroxidation product that provides a new mode of action for these biologically active fats.
Moreover, experiments on liposomes suggest that even after heavy peroxidation of the outer leaflet the inner leaflet is unaffected, indicating how cells may protect themselves from external peroxidation and maintain control over internal peroxidation.
Of the four major phospholipids naturally found in vertebrate membranes phosphatidylcholine and sphingomyelin are found primarily in the outer (extracellular facing) leaflet and phosphatidylethanolamine and phosphatidylserine in the inner (cytoplasmic facing) leaflet. Phosphatidylethanolamine and phosphatidylserine are the two major phospholipid classes that possess a large proportion of the highly polyunsaturated fatty acids.
This differential partitioning, combined with the inability of peroxidation to jump the leaflet divide in biological membranes, would act to protect highly polyunsaturated phospholipids from external initiated peroxidation and provide the cell with some control over peroxidation of phospholipids on the inner leaflet. This could partly explain how natural membranes protect themselves from exposures to initiators of peroxidation such as transition metals that are major players in numerous oxidative based diseases.