Lipid Peroxidation: an Overview

Lipid peroxidation (LPO) in cellular membranes is associated with changes in physicochemical properties and impairment of protein functions located in membrane environment. Recent studies shows involvement of LPO in biological signaling and various diseases. Lipids are oxidized by three distinct mechanisms: enzymatic oxidation; non-enzymatic, free radical-mediated oxidation and non-enzymatic, non radical oxidation. Lipids containing polyunsaturated fatty acids are susceptible to free radical-initiated oxidation and can participate in chain reactions that increase damage to biomolecules. Polyunsaturated fatty acids (PUFAs) and their metabolites have variety of physiological roles including: energy provision, membrane structure, cell signaling and regulation of gene expression. The present manuscript reviews concept of LPO with emphasis on implication in various diseases. INTRODUCTION: Lipids are heterogeneous groups of compound having significant role in various functions of body , when molecular oxygen reacts with unsaturated lipids catalysed by free radicals (nonenzymatic LPO) or enzymes (enzymatic LPO) 2, 3, 4 turning them rancid due to oxidative deterioration without releasing energy 1, 5 known as lipid peroxidation leads to cell damage by disturbance of fine structures, alteration of integrity, fluidity and functional loss of biomembranes and modifies low density lipoprotein (LDL) to proatherogenic and proinflammatory mediated potentially toxic products . LPO consists of three stages: initiation, propagation and termination 7 proceeded by three distinct methods: free radical-mediated oxidation; free radicalindependent, nonenzymatic oxidation and enzymatic oxidation 8 leads to damaging the biomolecules such as nucleic acids, proteins, structural carbohydrates and lipids The initiation phase of lipid peroxidation includes hydrogen atom abstraction by several radical species such as hydroxyl (•OH), alkoxyl (RO•), peroxyl (ROO•) and possibly HO2• . Polyunsaturated fatty acids (PUFA) in membrane lipids are susceptible to peroxidation because of abstraction of hydrogen atom from a methylene (–CH2–) group containing only one electron. Moreover, double bond weakens the C–H bonds on the nearby carbon atom facilitating the H• subtraction. The initial reaction of •OH with polyunsaturated fatty acids produces a lipid radical (L•), which in turn reacts with molecular oxygen to form a lipid peroxyl radical (LOO•). The LOO• can abstract hydrogen from an adjacent fatty acid to produce a lipid hydroperoxide (LOOH) and a second lipid radical . Further, reducing agents, such as Fe, causes reductive cleavage of LOOH producing lipid alkoxyl radical (LO•). The chain reaction of lipid peroxidation stimulated by both alkoxyl and peroxyl radicals by abstracting additional hydrogen atoms . Further mitochondrial injury can also results in generation of ROS induced by lipid