Several biomolecules, including PUFAs and some amino acids, cannot be made by human beings and must be supplied in the diet. These molecules are termed “essential dietary components” and serve as building blocks that are incorporated into larger structures such as proteins and cell membranes. PUFA membrane components are particularly vulnerable to damage (oxidation) by reactive oxygen species (ROS) as part of both normal and pathological
metabolism. Unlike catabolic oxidation of drugs, or oxidative damage to DNA or proteins (which occurs stoichiometrically), oxidation of PUFAs is particularly pernicious, proceeding through a non-enzymatic lipid peroxidation chain reaction (LPO), whereby a single ROS species can initiate a runaway autoxidation process that does not need any additional ROS to propagate.
LPO may damage hundreds to thousands of PUFA residues in PUFA-rich neuronal, mitochondrial and retinal membranes. The chain oxidation proceeds inexorably through multiple steps, destroying lipid membranes and generating highly reactive toxic secondary products that damage numerous biomolecules, such as proteins and DNA, irreversibly. This makes LPO one of the most detrimental processes that occur in the body. LPO is not controlled by enzymes, so evolution could not have provided a straightforward solution. Antioxidants cannot efficiently stop the incipient chain reaction because their maximal achievable concentration in lipid membranes is orders of magnitude lower than the PUFA concentration (typically, 1 tocopherol moiety per 2000 PUFA residues in a bilayer). Numerous neuronal and retinal diseases have LPO in their etiology. To put things in perspective, the brain makes up 1.5–2% of body weight yet consumes about a fifth of the body’s total energy output. A quarter of this 20%, i.e. 5% of the total body energy expenditure, is used by the brain to recycle damaged lipids in neuronal membranes.