Protein oxidation and peroxidation

Abstract

Proteins are major targets for radicals and two-electron oxidants in biological systems due to their abundance and high rate constants for reaction. With highly reactive radicals damage occurs at multiple side-chain and backbone sites. Less reactive species show greater selectivity with regard to the residues targeted and their spatial location. Modification can result in increased side-chain hydrophilicity, side-chain and backbone fragmentation, aggregation via covalent cross-linking or hydrophobic interactions, protein unfolding and altered conformation, altered interactions with biological partners and modified turnover. In the presence of O2, high yields of peroxyl radicals and peroxides (protein peroxidation) are formed; the latter account for up to 70% of the initial oxidant flux. Protein peroxides can oxidize both proteins and other targets. One-electron reduction results in additional radicals and chain reactions with alcohols and carbonyls as major products; the latter are commonly used markers of protein damage. Direct oxidation of cysteine (and less commonly) methionine residues is a major reaction; this is typically faster than with H2O2, and results in altered protein activity and function. Unlike H2O2, which is rapidly removed by protective enzymes, protein peroxides are only slowly removed, and catabolism is a major fate. Although turnover of modified proteins by proteasomal and lysosomal enzymes, and other proteases (e.g. mitochondrial Lon), can be efficient, protein hydroperoxides inhibit these pathways and this may contribute to the accumulation of modified proteins in cells. Available evidence supports an association between protein oxidation and multiple human pathologies, but whether this link is causal remains to be established.

Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability

“…Proteins are major targets for these oxidants as a result of their abundance, and high rate constants for reaction, with sulfur-containing amino acids being particularly prone to modification due to the presence of the reactive sulfur center (reviewed)151718. Oxidation of cysteine (Cys) and methionine (Met) residues is relatively well understood (reviewed)1920, but modification of disulfides (e.g.…”

Photosensitization of peptides and proteins by pterin derivatives

“…We have focused our attention on the chemical modifications of tyrosine (Tyr) and tryptophan (Trp) residues because these amino acids are particularly susceptible to a variety of oxidizing agents [26]. Moreover, the photosensitization of free Trp and Tyr by Ptr has previously been reported [12,13].…”

Effect of Reduction of Redox Modifications of Cys-Residues in the Na,K-ATPase α1-Subunit on Its Activity

“…Irreversible oxidation of cysteines of the protein to Cys-SO 3 H and Cys-SO 2 H was proposed as a marker for protein degradation by the cellular machinery [17] whereas oxidation to Cys-SOH is considered now as a posttranslational modification that can be important for enzyme regulation [18]. Treatment of Na,K-ATPase with reducing agents decreases the number of Cys-SOH and Cys-SO 2 H (Table 1) .…”