**5.2 Lipid peroxidation**

Lipid peroxidation is a free radical chain reaction that is comprised of three primary steps: initiation, propagation, and termination. Highly reactive radicals, such as the hydroxyl radical, attack polyunsaturated fatty acids, causing a hydrogen atom to be removed from the methylene (—CH2—) group and, thus, initiate lipid peroxidation. Polyunsaturated fatty acids are very sensitive to peroxidation, as the number of double bonds in the fatty acid side chain increases, the hydrogen atom cleavage becomes easier [13]. Conjugated dienes will, however, react to one another in the bounds of the membranes or other membrane components such as protein and cholesterol under conditions when O2 is extremely restricted [48]. The creation of conjugated dienes is followed by changes in the structure of the double bond from cis to trans form,

#### *Accenting Lipid Peroxidation*

which may facilitate tighter packing of the unsaturated fatty acids, contributing to the development of more rigid domains inside the bilayer of oxidized lipid [49].

When the hydrogen atom leaves the molecule by acquiring an electron, only one electron remains in the carbon of the fatty acid; In order to eliminate the weakening of the C-H bond in the carbon atom adjacent to the double bond, the carbon-centered radical forms the conjugated diene. Conjugated diene reacts with oxygen, causing the lipid peroxyl radical (LOO•); the lipid radical formed in this step is important because it starts a chain reaction by removing the hydrogen atom from another fatty acid. Peroxyl radicals show less reactive properties than •OH; however, they can reach farther regions. Peroxyl radicals can react with each other, attack membrane proteins or break hydrogen atoms from neighboring fatty acid chains, leading to the progression of lipid peroxidation chain reaction. Lipid peroxidation in biological membranes can lead to decreased membrane fluidity and membrane potential, increased permeability to H<sup>+</sup> and other ions, and disruption of organelle or cell integrity [13].

The termination process is the last stage of lipid peroxidation. During this process, LOOs either undergo a reciprocal causal nexus or self-destruct and in this way go on to form non-radical products. Despite their potential to breakdown when exposed to high temperatures or by contact with transitional metal ions, LOOH is a compound which remains stable at physiological temperatures [23]. The formed free radicals (LO•, LOO•) and electrophilic products (e.g. 4-hydroxynonenal) can react with neighboring membrane proteins as well as diffuse with distant molecules such as DNA [13].
