Precursors of GSH

The role of GSH in the in-vivo reduction of V(V) to V(IV) was examined by EPR in a study by Lu, Fantus and coworkers [65]. The results of this experiment are shown in Figure 8. In insulin-resistant adipocytes (with naturally lower GSH coneentrations, Resistant in Fig. 8) or in cells pretreated with buthionine sulfoxi-mine (BSO, a GSH-synthase inhibitor, GSH-synthase inhibited in Fig. 8), showed inereased sensitivity to vanadate-stimulated phosphorylation of insulin reeeptors. This result was consistent with EPR speetra showing a decreased intra-eellular eoneentration of vanadyl ions that do not promote phosphorylation. Addition of N-aeetylcysteine, a precursor of GSH synthesis, to the incubating cells, restored the amount of EPR-detected vanadyl ion within the cells to control levels (eompare Resistant + NAC to Resistant in Fig. 8). 

Insoluble residue was the most abundant product of penta-chlorothiophenol metabolism in peanut. The importance of this process is obviously dependent upon the presence of an active C-S lyase system. S-(Pentachlorophenyl)cysteine was also a precursor of insoluble residue in peanut, but the extent to which this involved pentachlorothlophenol as an intermediate was not determined. Additional studies are needed to determine if insoluble residues are commonly formed from GSH conjugates by other routes. 

Cysteine is the precursor of protein cysteine, GSH, and (in the plants studied) the sulfur moiety of methionine, and is therefore the major portal for organic reduced sulfur. 

These results also suggested that the pool of cysteine which serves as a precursor of cystathionine, GSH, and protein turns over much more rapidly than would be predicted on the basis of the total soluble cysteine content of the cells. This could be due to the location of a precursor pool, of about 1% of the total cysteine, in a specific compartment of the cell. 

The N6-aminyl nucleoside radical of dA (120) has also been produced from a photochemical precursor (121) but not within DNA (Scheme 47). Photolysis (315 it 2 nm) of phenyUiydrazone 121 in the presence of GSH (50 mM) provides a 73% yield of dA. In the absence of excess thiol, the yield of dA is reduced (32%) as expected and is accompanied by the radical recombination product resulting from the dimerization of 120. 

N-Acetyl-l-cysteine (NAC), another significant precursor of the GSH biosynthesis, has broadly been used as effective antioxidant in a form of nutritional supplement (Soloveva M. E et al 2007, Thibodeau P. A., et al 2001). At low concentrations, it is a powerful protector of a-l-antiproteinase against the enzyme inactivation by HOCl. NAC reacts with HO radicals and slowly with H O however, no reaction of this endobiotics with superoxide anion radical was detected [88]. 

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