Research Topic

Impact of lipid Peroxidation on the physiology and Pathophysiology of cell membranes

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The general process of lipid peroxidation consists of three stages: initiation, propagation, and termination. The initiation phase of lipid peroxidation includes hydrogen atom abstraction. Several species can abstract the first hydrogen atom and include the radicals: hydroxyl, alkoxyl, peroxyl, and possibly ...

The general process of lipid peroxidation consists of three stages: initiation, propagation, and termination. The initiation phase of lipid peroxidation includes hydrogen atom abstraction. Several species can abstract the first hydrogen atom and include the radicals: hydroxyl, alkoxyl, peroxyl, and possibly HO* 2 but not H 2O 2 or O 2- . The membrane lipids, mainly phospholipids, containing polyunsaturated fatty acids are predominantly susceptible to peroxidation because abstraction from a methylene (-CH2-) group of a hydrogen atom, which contains only one electron, leaves at the back an unpaired electron on the carbon, -*CH-. The presence of a double bond in the fatty acid weakens the C–H bonds on the carbon atom nearby to the double bond and thus facilitates 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 a neighboring fatty acid to produce a lipid hydroperoxide (LOOH) and a second lipid radical. The LOOH formed can suffer reductive cleavage by reduced metals, such as Fe++, producing lipid alkoxyl radical (LO*). Both alkoxyl and peroxyl radicals stimulate the chain reaction of lipid peroxidation by abstracting additional hydrogen atoms. Peroxidation of lipids can disturb the assembly of the membrane, causing changes in fluidity and permeability, alterations of ion transport and inhibition of metabolic processes. Injure to mitochondria induced by lipid peroxidation can direct to further ROS generation. In addition, LOOH can break down, frequently in the presence of reduced metals or ascorbate, to reactive aldehyde products, including malondialdehyde (MDA), 4-hydroxy-2-nonenal (HNE), 4-hydroxy-2-hexenal (4-HHE) and acrolein. A great variety of compounds are formed during lipid peroxidation of membrane phospholipids. Lipid peroxidation is one of the major outcomes of free radical-mediated injury to tissue. Peroxidation of fatty acyl groups occurs mostly in membrane phospholipids. Peroxidation of lipids can greatly alter the physicochemical properties of membrane lipid bilayers, resulting in severe cellular dysfunction. In addition, a variety of lipid byproducts are produced as a consequence of lipid peroxidation , some of which can exert adverse and/or beneficial biological effects.


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