Biological membranes, lipid peroxidation

Inhibition of biological membrane lipid peroxidation evaluated 366... 

Similar studies with f/-ans-4-hydroxy-2-none-nal (HNE, a cytotoxic byproduct of biological membrane lipid peroxidation), indicate that it is also metabolically activated by CYP2B1 and -2B4 to a reactive species that binds irreversibly to their prosthetic heme"". Unlike the mechanism-based inactivation by aromatic aldehydes, strucmral analyses of the corresponding heme adduct (MW 770) revealed that the reaction proceeds without deformylation and involves an acyl carbon radical that partitions between addition to the heme and formation of the carboxylic acid"". Together these findings suggest that the P450-mediated metabolic activation of aldehydes is a versatile process wherein the enzyme may be inactivated via mechanistically diverse heme modifications. 

Peroxidation of lipid molecules invariably changes or damages lipid molecular structure. In addition to the self-destructive nature of membrane lipid peroxidation, the aldehydes that are formed can cross-link proteins. When the damaged lipids are the constituents of biologic membranes, the cohesive lipid bilayer arrangement and stable structural organization is disrupted (see Fig. 24.7). Disruption of mitochondrial membrane integrity may result in further free radical production. 

Vladimirov, Yu. A. Archakov, A. I. Lipid Peroxidation in Biological Membranes (in Russian), Nauka, Moscow, 1972... 

In the previous section, we have described some of the mechanisms that may lead to the fijrmation of lipid hydroperoxides or peroxyl radicals in lipids. If the peroxyl radical is formed, then this will lead to propagation if no chain-breaking antioxidants are present (Scheme 2.1). However, in many biological situations chain-breaking antioxidants are present, for example, in LDL, and these will terminate the peroxyl radical and are consumed in the process. This will concomitandy increase the size of the peroxide pool in the membrane or lipoprotein. Such peroxides may be metabolized by the glutathione peroxidases in a cellular environment but are probably more stable in the plasma comjxutment. In the next section, the promotion of lipid peroxidation if the lipid peroxides encounter a transition metal will be considered. 

UV-induced ROS are extremely toxic to cells by causing oxidative damage to all biomolecules (Sies 1991). For instance, lipids, which are major compounds of all biological membranes, may be destroyed by ROS. After a first initiation reaction an unsaturated fatty acid is converted to a peroxyl radical, which in turn attacks another unsaturated fatty acid finally leading to free radical cascades. This photochemical peroxidation of unsaturated fatty acids may be particularly damaging for membrane structure and function (Bischof et al 2006a). 

Superoxide has a chemical half-life measured in microseconds, but in even this short time serious damage can be caused to all types of biological macromolecules. Peroxidation of membrane lipids could cause haemolysis but the oxidation of ferrous (Fe2+) to ferric (Fe3+) iron in haemoglobin due to free radical action is a more immediate cause for concern within the red cell (Figure 5.17). 

Vitamin E resides in the lipid domain of biological membranes and plasma lipoprotein, where it prevents lipid peroxidation of PUFA. Because vitamin E is the most important antioxidant for... 

Inhibited Fe2 +-induced lipid peroxidation of biological membranes 366... 

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