ABSTRACT
Lipid peroxidation has been implicated in the pathogenesis of numerous diseases, including atherosclerosis, diabetes, cancer, and rheumatoid arthritis, as well as in drug-associated toxicity, postischemic reoxygenation injury, and aging. Lipid peroxidation proceeds by a free radical chain reaction mechanism and yields lipid hydroperoxides as the major initial reaction products (Figure 6.1). The lipid hydroperoxides further undergo carbon-carbon bond cleavage via alkoxyl radicals in the presence of transition metals giving rise to the formation of short-chain, unesteri-ed aldehydes of 3-9 carbons in length, and a second class of aldehydes still esteri-ed to the parent lipid (Esterbauer et al., 1991). The important agents that give rise to the modication of a protein may be represented by reactive aldehydic intermediates, such as 2-alkenals, and 4-hydroxy-2-alkenals (Esterbauer et al., 1991; Uchida,
Introduction ............................................................................................................ 119 Reactive Species Involved in Protein Lipoxidation ............................................... 120
Lipid Hydroperoxides ....................................................................................... 121 Aldehydes .......................................................................................................... 121
2-Alkenals .................................................................................................... 121 4-Hydroxy-2-Alkenals .................................................................................. 122 Ketoaldehydes .............................................................................................. 122 4-Hydroperoxy-2-Alkenals .......................................................................... 122
Protein Lipoxidation .............................................................................................. 123 Protein Oxidation .............................................................................................. 123 Protein Adduction.............................................................................................. 123
2-Alkenal Adducts ........................................................................................ 123 4-Hydroxy-2-Alkenal Adducts ..................................................................... 125 Ketoaldehyde Adducts .................................................................................. 126
Hydroperoxide-Dependent Protein Adduction ...................................................... 128 Protein Lipoxidation by 2-Alkanals in the Presence of Hydroperoxides .......... 128 Protein Lipoxidation by 4-Hydroperoxy-2-Alkenals ........................................ 129
Ligand Function of Lipoxidation Products ............................................................ 129 Conclusion ............................................................................................................. 129 Abbreviations ......................................................................................................... 130 References .............................................................................................................. 130
2003). These reactive aldehydes are considered important mediators of cell damage due to their ability to covalently modify biomolecules, which can disrupt important cellular functions and can cause mutations (Esterbauer et al., 1991). The most sensitive cellular target of the lipid peroxidation products is protein, generating a variety of covalent adducts (“protein lipoxidation”). The pattern of protein lipoxidation tends to be broad and incompletely resolved upon SDS-gel electrophoresis, due probably to the varying degrees of oxidative cleavage of the polypeptide chain and the modication of amino acid side chains. The protein lipoxidation is also associated with the introduction of carbonyl groups into amino acid residues, which is also mediated by a variety of modication pathways in vivo and in vitro, such as metal-catalyzed oxidation of specic amino acid residues and glycation.
