Transition metals interactions with lipid

Compounds such as superoxide anion and peroxides do not directly interact with lipids to initiate oxidation they interact with metals or oxygen to form reactive species. Superoxide anion is produced by the addition of an electron to the molecular oxygen. It participates in oxidative reactions because it can maintain transition metals in their active reduced state, can promote the release of metals that are bound to proteins, and can form the conjugated acid, perhydroxyl radical depending on pH, which is a catalyst of lipid oxidation (39). The enzyme superoxide dismu-tase that is found in tissues catalyzes the conversion of superoxide anion to hydrogen peroxide. 

The interfacial thickness of emulsion droplets is an important parameter affecting lipid oxidation reaction rates. Increasing interfacial membrane thickness can conceivably hinder the physical interaction between aqueous phase prooxidants (e.g., transition metals) and emulsified lipids(Chaiyasit et al., 2000 Silvestre et al., 2000). For example, Silvestre and co-workers (2000) showed that iron-catalyzed cumenehydroperoxide reduction, as well as salmon oil-in-water emulsion oxidation, was slower when Brij 700 was used in place of Brij 76. Brij 700 and 76 are small molecule surfactants with identical hydrophobic tail group lengths (CHjlCH lj -), but vary only with respect to the size of their polar head groups Brij 700 and Brij 76 consist of 100 and 10 oxyethylene head groups, respectively. Lower hydroperoxide decomposition and lipid oxidation rates in Brij 700-stabilized emulsions suggest that a thicker interfacial layer was able to act as a physical barrier to decrease lipid-prooxidant interactions (Silvestre et al., 2000). 

In this reaction scheme, the steady-state concentration of peroxyl radicals will be a direa function of the concentration of the transition metal and lipid peroxide content of the LDL particle, and will increase as the reaction proceeds. Scheme 2.2 is a diagrammatic representation of the redox interactions between copper, lipid hydroperoxides and lipid in the presence of a chain-breaking antioxidant. For the sake of clarity, the reaction involving the regeneration of the oxidized form of copper (Reaction 2.9) has been omitted. The first step is the independent decomposition of the Upid hydroperoxide to form the peroxyl radical. This may be terminated by reaction with an antioxidant, AH, but the lipid peroxide formed will contribute to the peroxide pool. It is evident from this scheme that the efficacy of a chain-breaking antioxidant in this scheme will be highly dependent on the initial size of the peroxide pool. In the section describing the copper-dependent oxidation of LDL (Section 2.6.1), the implications of this idea will be pursued further. 

In 1988 Bast and Haenen [201] reported that both LA and DHLA did not affect iron-stimulated microsomal lipid peroxidation. However, Scholich et al. [202] found that DHLA inhibited NADPH-stimulated microsomal lipid peroxidation in the presence of iron-ADP complex. Inhibitory effect was observed only in the presence of a-tocopherol, suggesting that some interaction takes place between these two antioxidants. Stimulatory and inhibitory effects of DHLA have also been shown in other transition metal-stimulated lipid peroxidation systems [203,204]. Later on, the ability of DHLA (but not LA) to react with water-soluble and lipid-soluble peroxyl radicals has been proven [205], But it is possible that the double (stimulatory and inhibitory) effect of DHLA on lipid peroxidation originates from subsequent reactions of the DHLA free radical, capable of participating in new initiating processes. 

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