Protein oxidation reactive oxygen species reactivity with amino

Metal ions lead to protein oxidation either by reacting directly with an amino acid to form a radical, or by generating reactive oxygen species in solution. Amino acids that chelate transition metal ions (e.g., histidine) are most prone to metal-catalyzed oxidation because the complex generates the reactive oxygen species that lead to oxidation.The proximity of the nascent reactive oxygen species to the chelated amino acid makes that amino acid most susceptible to attack. 

The other amino acid residue present in proteins that is susceptible to oxidation is the indole moiety of tryptophan (Fig. 11). The reducing potential of tryptophan is considerably less than that of cysteine and methionine, so oxidation of tryptophanyl residues usually does not occur until all exposed thiol residues are oxidized. Also, the spontaneous oxidation of tryptophanyl residues in proteins is much less probable than that of cysteinyl and methionyl residues. Tryptophan residues are the only chromophoric moieties in proteins which can be photooxi-dized to tryptophanyl radicals by solar UV radiation, even by wavelengths as long as 305 nm (B12). Tryptophanyl residues readily react with all reactive oxygen species, hypochlorite, peroxynitrite, and chloramines. Oxidative modifications of other amino acid residues require use of strong oxidants, which eventually are produced in the cells. Detailed mechanisms of action of these oxidants is described in subsequent sections of this chapter. 

Several amino acyl constituents crucial for the protein s function are particularly vulnerable to radical damage (Roshchupkin et al., 1979 Singh et al., 1982 Sies, 1986), as shown in Scheme 2.2 and Table 2.2, with the consequences of oxidative modification. It is generally accepted that reactive oxygen species can react directly at several of these sites on a protein in addition, in some instances, when protein radicals are formed at a specific amino acyl site, they can be rapidly transferred to other sites within the protein infrastructure, the pathway so far proven being illustrated in Fig. 2.14 (Butler et al., 1988). 

Fig. 7. Oxidation products of proteins. The vertical structure in the middle represents the main peptide chain with amino acid side groups extending horizontally (M2). The a-carbons in the primary chain can be oxidized to form hydroperoxides. Reactions on the right side near the top exemplify oxidation of the primary chain leading to a peroxyl radical. Side chains represented are lysine, methionine, tyrosine, cysteine, and histidine, top to bottom, respectively. Modifications of the side chains and primary chain lead to carbonyl formation and charge modifications. If these reactions are not detoxified by antioxidants, they may propagate chain reactions within the primary chain, leading to fragmentation of the protein. See the text for details, o, represents reaction with oxygen RNS, reactive nitrogen species ROS, reactive oxygen species. Dense dot represents unpaired electron of radical forms.

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