PUFA radical

Damage to cell membranes may be initiated by the reaction of the hydroxyl radical with a PUFA, generating a PUPA radical. The hydroxyl radical is converted to water (Figure 9.91). The PUFA radical, in turn, can be repaired by vitamin E (Figure 9.92). Involvement of vitamin E in this repair results in its conversion to a vitamin E radical. The vitamin E radical is relatively unreactive and does not cause further damage to the cell. In the absence of vitamin E, the PUFA radical may induce a chain reaction, resulting in widespread damage to cell membranes. 

Lipid Analyses. Verification of PUFA radical chain reactions induced by light-activated DPE molecules can be made by examining changes in a polar lipid fraction collected from injured tissues. Radical chain reactions can be terminated through cross-reactions of the endoperoxides formed (48). Therefore, either an appearance of lipid polymers or disappearance of certain phospholipids should occur. If only the PUFA moieties are involved in these reactions, a loss of PUFA in the DPE-treated tissue or an increase in the ratio of saturated to unsaturated fatty acids should occur. 

Spin-trapping techniques have been used to study reactions of lipoxygenase with linoleic acid ( ). It was proposed that the formation of dimeric linoleic acid required the involvement of hydroperoxylinoleic acid ( ). The ESR spectrum from the interactions of the PUFA radical and the spin-trap indicated this involvement occurred Similar spin-trapping techniques could be used to investigate the possibility that DPE s may ultimately induce formation of various fatty acid dimers (e.g., dimers of linolenic acid). Formation of such polymers should dramatically affect membrane function. 

Figure 45-6. Interaction and synergism between antioxidant systems operating in the lipid phase (membranes) of the cell and the aqueous phase (cytosol). (R-,free radical PUFA-00-, peroxyl free radical of polyunsaturated fatty acid in membrane phospholipid PUFA-OOH, hydroperoxy polyunsaturated fatty acid in membrane phospholipid released as hydroperoxy free fatty acid into cytosol by the action of phospholipase Aj PUFA-OH, hydroxy polyunsaturated fatty acid TocOH, vitamin E (a-tocopherol) TocO, free radical of a-tocopherol Se, selenium GSH, reduced glutathione GS-SG, oxidized glutathione, which is returned to the reduced state after reaction with NADPH catalyzed by glutathione reductase PUFA-H, polyunsaturated fatty acid.)...

Lipid peroxidation is a radical-mediated chain reaction resulting in the degradation of polyunsaturated fatty acids (PUFAs) that contain more than two covalent carbon-carbon double bonds (reviewed by Esterbauer et al., 1992). One of the major carriers of plasma lipids is LDL, a spherical molecule with a molecular weight of 2.5x10 . A single LDL particle contains 1300 PUFA molecules (2700 total fatty-acid molecules) and is... 

The active enzyme abstracts a hydrogen atom stereospecifically from the intervening methylene group of a PUFA in a rate-limiting step, with the iron being reduced to Fe(II). The enzyme-alkyl radical complex is then oxidized by molecular oxygen to an enzyme-peroxy radical complex under aerobic conditions, before the electron is transferred from the ferrous atom to the peroxy group. Protonation and dissociation from... 

FIGURE 32-6 Lipid peroxidation leads to fragmentation or oxidation of polyunsaturated fatty acids (PUFA). HO, hydroxyl radical LO, lipid alkoxylradical LOO, lipid peroxyl radical 0 2, superoxide radical O, atomic oxygen radical. (From Hall in [3].)... 

Qian, S. Y., Wang, H. P., Schafer, F. Q., and Buettner, G. R., 2000, FPR detection ofhpid-derived free radicals from PUFA, LDL, and cell oxidations. Free Radio. Biol. Med 29 568-579. 

The other important property affecting lipid oxidation is the chelating effect of chlorogenic acids. It is important to keep in mind that the influence of biometals (Fe, Cu etc.) on lipid free radical oxidation is essential. It is well known that iron can react with hydrogen peroxide by the Fenton reaction (Equation 3). The hydroxyl radical formed in the Fenton reaction is capable of reacting with lipid and PUFA as the initiation stage. Iron can also participate in alkyl peroxide or lipid peroxide decomposition. Therefore, the nature of iron chelation in a biological system is an important aspect in disease prevention. 

Thus, 26 molecules of linoleic acid undergo autoxidation when a single free radical is introduced into this model membrane system (96). That much damage might well be enough to destroy the membrane and produce cell lysis and death however, we must remember that in the real system, the polyunsaturated fatty acids (PUFA) would be protected by antioxidants such as vitamin E. 

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