S-thiolation

S-Thiolation of proteins may occur by two main processes as shown in Fig. 4.14. The first relies on an increase in GSSG levels while the second method depends on free radical production and the GSH concentration (Miller et al., 1990). Therefore, it is clear that a significant increase in tissue GSSG levels is not an absolute prerequisite for S-thiolation to occur. 

If cellular redox state, determined by the glutathione status of the heart, plays a role in the modulation of ion transporter activity in cardiac tissue, it is important to identify possible mechanisms by which these effects are mediated. Protein S-,thiolation is a process that was originally used to describe the formation of adducts of proteins with low molecular thiols such as glutathione (Miller etal., 1990). In view of the significant alterations of cardiac glutathione status (GSH and GSSG) and ion-transporter activity during oxidant stress, the process of S-thiolation may be responsible for modifications of protein structure and function. 

Figure 4.14 Diagrammatic representation of (a) oxy-radical>mediated S-thioiation and (b) thiol/disulphide-initiated S-thiolation of protein suiphydryl groups. Under both circumstances mixed disuiphides are formed between glutathione and protein thiois iocated on the ion-translocator protein resulting in an alteration of protein structure and function. Both of these mechanisms are completely reversible by the addition of a suitabie reducing agent, such as reduced glutathione, returning the protein to its native form.

Miller, R.M., Sies, H., Park, E.-M. and Thomas, J.A. (1990). Phosphorylase and creatine kinase modification by thiol-disulphide exchange and by xanthine oxidase-initiated S-thiolation. Arch. Biochem. Biophys. 276, 355-363. 

Cobalt, Co2+ d1) 4, tetrahedral S-Thiolate, thioether, V-i midazole Alkyl group transfer, oxidases... 

Methylation of aldehydes and ketones.1 Unlike Grignard and alkyllithium reagents, this reagent does not react with esters, S-thiolates, nitriles, and epoxides, but does react with aldehydes even at — 70 to — 20 and ketones at — 25 to — 80° at reasonable rates. Reaction of 1 with 4-t-bulylcyclohexanone results in the corresponding adducts in the ratio cis/trans = 85 15. 

Ravichandran V, Seres T, Moriguchi T, Thomas J A, Johnston RB, Jr. 1994. S-thiolation of glyceraldehyde-3-phosphate dehydrogenase induced by the phagocytosis-associated respiratory burst in blood monocytes. J Biol Chem 269 25010-25015. 

The [Mo(NO)(S4)] fragment yielded a series of three complexes with formal 16, 17, and 18 VE counts (Fig. 10). Although the chloro complex [Mo(C1)(NO)(S4)] potentially can be considered an 18 VE species due to n donation from the chloride ion (see above), the different electronic situations in the three complexes are clearly reflected by the v(NO) frequencies. However, there are no antibonding electrons, and the Mo— S (and other Mo donor) bond distances stay in the usual range. In addition, while Mo—S(thiolate) and Mo—S(thioether) distances in different [Mo(S4)] complexes can vary considerably, the respective Mo—S distances in [Mo(C1)(NO)(S4)J, [Mo(PMe3)(NO)-(S4)], and [Mo(NO)2(S4)] are very similar. Figure 10 summarizes these results and correlations (108, 109). 

A different rendering of the relevant core atoms of the dication [Fe, N2H2, S(thiolate) donors] shows that the dicationic diazene complex B and the N2 complex C are potential redox isomers or valence tautomers (Scheme 38). 

A large number of enzyme activities have been shown to be affected by protein S-thiolation with glutathione redox buffers in vitro (reviewed in ref. [271]). Extracellular and cell-surface proteins are commonly activated by the formation of intramolecular disulfides. Conversely, most of the responsive intracellular enzymes are down-regulated by the formation of mixed disulfides, with the interesting exception of enzymes involved in the delivery of free glucose. 

Thus, Nature has integrated thiol/disulfide exchange reactions in the regulation of its metabolic and antioxidant networks. The potentially cytotoxic effects of protein S-thiolation will remain controversial until the relationship between the systems of glutathione reductase, thioredoxin, glutaredoxin and thioltransferase are better understood. 

Dl. Dafre, A. L., and Reischl, E., Oxidative stress causes intracellular reversible S-thiolation of chicken hemoglobin under diamide and xanthine oxidase treatment. Arch. Biochem. Biophys. 358,291-296(1998). 

G21. Grant, C. M., Quinn, K. A., and Dawes, I. W., Differential protein S-thiolation of glyceraldehyde-3-phosphate dehydrogenase isoenzymes influences sensitivity to oxidative stress. Mol. Cell Biol. 19, 2650-2656 (1999). 

P3. Padgett, C. M., and Whorton, A. R., Cellular responses to nitric oxide Role of protein S-thiolation/dethiolation. Arch. Biochem. Biophys. 358,232—242 (1998). 

R12. Rokutan, K., Thomas, J. A., and Johnston, R. B. J., Phagocytosis and stimulation of the respiratory burst by phorbol diester initiate S-thiolation of specific proteins in macrophages. J. Immunol. 147, 260-264 (1991). 

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