Thiol proteins, oxidation

From a broader perspective, protein oxidation can result in covalent modification at many sites other than just at cysteine thiols. The earliest reports on protein oxidation date from the first decade of the twentieth century, but it took many more years to characterize these reactions and their products (Dakin, 1906). 

Thiols, protein or small molecular weight, can be S-nitrosated either by reaction with N O-oxidation products (Scheme 4.1) in hydrophobic domains of plasma proteins or transnitrosated at the cell-plasma interface of NO-producing cells (endothelial cells) or NO-storing cells (RBCs). Efforts to determine the true levels in plasma and in the various cellular compartments are complicated owing to thermal sensitivity and photosensitivity (Sexton et al., 1994 Alpert et al., 1997 Mutus et al., 1999) of the RS-NO bond. Techniques currently employed for the detection and quantification of RSNOs have been summarized in recent reviews (Martinez Riuz and Lamas, 2004 Rasaf et al., 2004). 

Beer, S.M., Taylor, E.R., Brown, S.E., Dahm, C.C., Costa, N.J., Runswick, M.J., and Murphy, M.P. 2004. Glutaredoxin 2 catalyzes the reversible oxidation and glutathionylation of mitochondrial membrane thiol proteins implications for mitochondrial redox regulation and antioxidant defence. J. Biol. Chem. 279 47939-47951. 

Glutathionylated proteins can be formed by the interaction of nitric oxide and protein thiols. For example, exposure of mitochondria to NO can lead to the formation of peroxynitrite, an oxidant, that can cause protein glutathionylation. Protein glutathionylation may also occur via the formation of a nitroso thiol protein (PrSNO) followed by the glutathionylate anion displacement of the nitroxyl anion (NO-) by GSH to form protein glutathionylation as shown in Figure 18.13. 

AO/FRS - scavenges OH, HOC1 i Fe(II)- Cu(II)-dependent lipid OH generation from H202, FA oxidation protein oxidation AO (per glutathione-S-transferase induction) AO/FRS - scavenges 02-, NOV [keeps thiols reduced in cytosol]... 

Gallenbeck et al. (25) has summarized the work on reductive alkylation using formaldehyde and sodium borohydride to yield dimethylated proteins. Oxidation and reduction reactions involving thiol and disulfide groups have been discussed by Ryan (13) and Feeney (11). 

It can nonenzymatically reduce substances, such as peroxides or free radicals, which accumulate in cells under oxidizing conditions. By maintaining an intracellular reducing environment, glutathione prevents intracellular protein thiols from oxidizing to disulfides. 

Two reactions of the —SH group are important in the chemistry of proteins. When thiols are oxidized by agents such as O2, a coupling reaction occurs (two molecules become one) to form a disulfide, a compound containing an —S—S— linkage ... 

Many of the chemical properties of thiols stem from the fact that the sulfur atom of a thiol is oxidized easily to several higher oxidation states. The most common reaction of thiols in biological systems is their oxidation to disulfides, the functional group of which is a disulfide (—S—S —) bond. Thiols are readily oxidized to disulfides by molecular oxygen. In fact, they are so susceptible to oxidation that they must be protected from contact with air during storage. Disulfides, in turn, are easily reduced to thiols by several reagents. This easy interconversion between thiols and disulfides is very important in protein chemistry, as we will see in Chapter 18 ... 

The addition of thiol or amino groups of proteins, e.g., HS-groups of L-cysteine or -amino groups of L-lysine residues, to the quinoid structures yields covalent bindings between melanins and proteins. Oxidative cleavage of the quinoid rings causes formation of pyrrol moieties, which are frequently part of the melanin molecule (Fig. 290). 

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