Dehydroascorbic acid glutathione reductase

Washburn, M.P., and Wells, W.W. 1999. Identification of the dehydroascorbic acid reductase and thioltransferase (glutaredoxin) activities of bovine erythrocyte glutathione peroxidase. Biochem. Biophys. Res. Commun. 257 567-571. 

These differences are correlated with differing functions. The intracellular reduced thioredoxins are thermodynamically the best reductants of disulfide linkages in proteins and they help keep intracellular proteins reduced. Glutaredoxin can be reduced efficiently by reduced glutathione or by NADPH and glutathione reductase and can, in turn, reduce cysteine and the oxidized form of vitamin C, dehydroascorbic acid (Box The peri-... 

Spinach leaves contain a dehydroascorbate reductase enzyme that catalyzes Reaction 13 at acidic and neutral pH values, but the enzyme is not, located within the chloroplast (73-76). GSSG produced by Reaction 13 can be re-converted to GSH by glutathione reductase, an enzyme located in the chloroplast (77). 

FIGURE 12. The regeneration of ascorbic acid from dehydroascorbic acid by an enzymic and non-enzymatic mechanism. Dehydroascorbate reductase, using glutathione (GSH) as a cofactor, can regenerate ascorbic acid (ASA) from dehydroascorbic acid (DHAA) intracellularly. In an extracellular environment, DHAA reduction by GSH may occur nonenzymatically. Adapted from Bode et al. (1993). 

It has been known for some time that there exists a close correlation between the ascorbic acid and glutathione content of plant tissues. Plant tissues are also known to contain dehydroascorbic reductase, which catalyzes the transfer of hydrogens from GSH to dehydroascorbic acid, as well as ascorbic acid oxidase. Mapson and Goddard have, therefore, provided a possible scheme for hydrogen transport which does not involve the cytochrome system. The hydrogens may take the following pathway ... 

This reaction would not be expected to be reversible since the oxidation-reduction potential of ascorbate is more positive than that of GSH. Plants contain ascorbic acid reductase an enzyme which catalyzes the above reaction (109, 110), while animal tissues do not possess this enzyme. The nonenzymic oxidation of GSH by dehydroascorbate is sufficiently rapid however to be of biological significance and could under certain conditions act as an oxidizing system of TPNH via glutathione reductase. 

As shown in Figure 13.3, oxidation of ascorbic acid, for example, by the reduction of superoxide to hydrogen peroxide or Fe + to Fe +, and similar reduction of other transition metal ions, proceeds by a one-electron process, forming the monodehydroascorbate radical. The radical rapidly disproportionates into ascorbate and dehydroascorbate. Most tissues also have both nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione-dependent monodehydroascorbate reductases, which reduce the radical back to ascorbate. Ascorbate is thus an effective quencher of singlet oxygen and other radicals. 

Fig. 7.8 Top half of the figure depicts the spontaneous oxidation of ascorbate by oxygen-free radicals, peroxides and proline hydroxylase (black arrow) and the reduction of dehydroascorbate to ascorbate by dehydroascorbate via PDI, or providing reducing equivalents as a cofactor for peroxidases and other reductases (upper and lower red arrows). The oxidized form (GSSG) is reduced by NADPH (straight blue arrow). (Slightly modified from Meister A., Glutathione-ascorbic acid antioxidant system in animals. J. Biol. Chem., 269(13) 9397-9400,1994)...

As shown in Figure 1, oxidation of ascorbic acid proceeds by a one-electron process, forming mono-dehydroascorbate, which disproportionates to ascorbate and dehydroascorbate. Most tissues also contain monodehydroascorbate reductase (EC 1.6.5.4), a flavoprotein that reduces the radical back to ascorbate. Dehydroascorbate is reduced to ascorbate by dehydroascorbate reductase (EC 1.8.5.1), a glutathione-dependent enzyme little is oxidized to diketogulonic acid in human beings. 

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