Protein oxidation repair

Conversion of epoxides (arene oxides) into phenols is spontaneous. The conversion of epoxides into dihydrodiols is catalyzed by EH (EC 4.2.1.63). Hydroxyl containing PAHs can act as substrates for conjugases (C) (UDP glucuronsyl transferase (EC 2.4.1.17) and phenol sulphotransferase (EC 2.8.2.1)). This pathway usually leads to inactive excretable products. Epoxides are scavenged by GSH and the reaction is catalyzed by GSHt (EC 2.5.1.18). When GSH is depleted and/or the other pathways are saturated, epoxides of dihydrodiols (particularly 7,8-diol-9,10-epoxides in the case of BP) and phenol metabolites react with cellular macromolecules such as DNA, RNA, and protein. If repair mechanisms are exceeded the detrimental effects of PAH may result. 

Keywords Proteasome Protein oxidation Protein degradation Protein repair... 

Thus numerous changes in the protein pool occur due to oxidation, depending on the acting oxidant and presence and accessibility of oxidizable amino acid residues in the protein molecule. Very often these protein modifications are accompanied by a loss of normal protein function and in some case the acquiring of new pathological functions (gain of function). Oxidative modifications result in modification of the susceptibility to protein degradation and, in the case of extracellular proteins, in altered uptake rates. One has to take into account that the oxidation state of the protein pool is the result of two components protein oxidation and the repair or removal of these oxidized protein forms. 

Protein oxidation is considered to be one of the important processes during oxidative stress. Once oxidative stress occurs protein oxidation takes place. The measurable changes in the protein pool are always the result of the protein oxidation process itself, protein repair, and the degradation of oxidized proteins (Fig. 11). Cells are able to recover from protein oxidation, mostly by a selective degradation of the oxidized proteins. However, during the lifetime and in certain diseases the removal of oxidized proteins is sub-optimal and therefore proteins accumulate and interfere with the cellular metabohsm. 

Fan, Z., Beresford, P. J., Zhang, D., Xu, Z., Novina, C. D., Yoshida, A., Pommier, Y., and Lieberman, J. (2003). Cleaving the oxidative repair protein Apel enhances cell death mediated by granzyme A. Nature Immunol. 4, 145-153. 

The findings discussed above suggest that the presence of Met(O) residues in a-l-PI and lens proteins might account for some of the observed clinical manifestations. It is of interest to speculate that Met(0)-peptide reductase may function as a repair enzyme to prevent the accumulation of Met(O) residues in most proteins. Whether in those examples as discussed above, the accumulation of Met(O) in proteins is a result of an overwhelming increase in the synthesis of biological oxidants and/or a decrease in the ability to either destroy the biological oxidants or reduce the Met(O) residues in the proteins is not known. If it is the latter, this could be due to a decrease in the reductase itself or to some impairment in the reducing system that the enzyme requires. 

DNA CT also permits chemistry at a distance. Oxidative DNA damage and thymine dimer repair can proceed in a DNA-mediated reaction initiated from a remote site. These reactions too are sensitive to intervening DNA dynamical structure, and such structures can serve to modulate DNA CT chemistry. The sensitivity of DNA CT to base pair stacking also provides the basis for the design of new DNA diagnostics, tools to detect mutations in DNA and to probe protein-DNA interactions. 

In contrast to nucleic acids, which can be repaired after oxidative damage by excision and insertion mechanisms (see Chapter 28), the repair of oxidized proteins does not occur except the oxidized sulfur-containing amino acid residues [22]. Instead, oxidized proteins are... 

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