The glutathione-ascorbate cycle is a metabolic pathway that detoxifies hydrogen peroxide (H2O2), which is a reactive oxygen species that is produced as a waste product in metabolism. The cycle involves the antioxidant metabolites: ascorbate, glutathione and NADPH and the enzymes linking these metabolites.
In the first step of this pathway, H2O2 is reduced to water by ascorbate peroxidase (APX) using ascorbate as the electron donor. The oxidized ascorbate (monodehydroascorbate) is regenerated by monodehydroascorbate reductase (MDAR). However, monodehydroascorbate is a radical and if not rapidly reduced it disproportionates into ascorbate and dehydroascorbate. Dehydroascorbate is reduced to ascorbate by dehydroascorbate reductase at the expense of GSH, yielding oxidized glutathione (GSSG). Finally GSSG is reduced by glutathione reductase (GR) using NADPH as electron donor. Thus ascorbate and glutathione are not consumed; the net electron flow is from NADPH to H2O2. The reduction of dehydroascorbate may be non-enzymatic or catalysed by proteins with dehydroascorbate reductase (DHAR) activity, such as glutathione S-transferase omega 1 or glutaredoxins.
In plants, the glutathione-ascorbate cycle operates in the cytosol, mitochondria, plastids and peroxisomes. Since glutathione, ascorbate and NADPH are present in high concentrations in plant cells it is assumed that the glutathione-ascorbate cycle plays a key role for H2O2 detoxification. Nevertheless, other enzymes (peroxidases) including peroxiredoxins and glutathione peroxidases, which use thioredoxins or glutaredoxins as reducing substrates, also contribute to H2O2 removal in plants.
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