Ascorbate-glutathione cycle

In contrast, antioxidant enzymes can efficiently counteract all UV-induced ROS (Aguilera et al. 2002). These enzymes are represented by superoxide dismutase (SOD), catalase and glutathione peroxidase as well as those involved in the ascorbate-glutathione cycle, such as ascorbate peroxidase, mono-dehydroascorbate reductase, dehydroascorbate reductase and glutathione reductase. One of the most important classes of antioxidant enzymes is the SOD family, which eliminate noxious superoxide radical anions. Different metalloforms of SOD exist (Fe, Mn, CuZn and Ni), which due to their intracellular localisation protect different cellular proteins (Lesser and Stochaj 1990). 

Jimenez, A., Hernandez, J. A., del Rio, L. A., and Sevilla, F., 1997, Evidence for the presence of the ascorbate-glutathione cycle in mitochondria and peroxisomes of pea leaves. Plant Physiol. 114 275n284. 

Figure 3. An ascorbate-glutathione cycle for removal of H2O2 in illuminated chloroplasts.

After this paper was submitted, further evidence for the operation of an ascorbate-glutathione cycle in spinach (85) and pea (86) chloroplasts was reported. The original failure to detect this cycle in pea... 

Fig. 14. The ascorbate-glutathione cycle. APX - ascorbate peroxidase DMA - dehydroascorbate DHAR - dehydroascorbate reductase OR - glutthione reductase GSH - reduced glutathione GSSG - glutathione disulfide MDHR - monodehydroascorbate reductase.

The removal of superoxide dismutase-generated H2O2 within the chloroplast is accomplished via ascorbate and glutathione and the linked enzymes ascorbate peroxidase, dehydroascorbate reductase, and glutathione reductase. Generally, it is referred to as the ascorbate-glutathione cycle. " ... 

NADPH dehydrogenases, ascorbate peroxidase (APX), glutathione reductase (GR), the ascorbate-glutathione cycle, and several small molecules can scavenge or neutralize oxygen radicals. Under normal conditions, the formation and neutralization of ROS is balanced. Under stress, however, an imbalance leads to accumulation of ROS, to oxidative stress. 

Reactive oxygen species (ROS) and other radicals are effectively quenched by carotenoids, tocopherols, ascorbate, and reduced glutathione, supported by antioxidant enzymes, including superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), and the enzymes involved in the ascorbate-glutathione cycle to detoxify ROS, such as ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and glutathione reductase (GR). " ... 

In addition to the well-known iron effects on peroxidative processes, there are also other mechanisms of iron-initiated free radical damage, one of them, the effect of iron ions on calcium metabolism. It has been shown that an increase in free cytosolic calcium may affect cellular redox balance. Stoyanovsky and Cederbaum [174] showed that in the presence of NADPH or ascorbic acid iron ions induced calcium release from liver microsomes. Calcium release occurred only under aerobic conditions and was inhibited by antioxidants Trolox C, glutathione, and ascorbate. It was suggested that the activation of calcium releasing channels by the redox cycling of iron ions may be an important factor in the stimulation of various hepatic disorders in humans with iron overload. 

In this classical Haber-Weiss cycle iron is being reduced by superoxide anion radical (02T), ascorbic acid or glutathione and subsequently decomposes hydrogen peroxide - formed by spontaneous dismutation of 02T - in the Fenton reaction to produce 0H. This iron-driven 0H formation has a stringent requirement for an available iron coordination site, a sine qua non met not only by hexaaquoiron(III) but by most iron chelates (28). Thus, Fe-EDTA, -EGTA, and -ATP retain a reactive coordination site and catalyze the Haber-Weiss cycle. Phytic acid, however, occupies all available iron coordination sites and consequently fails to support 0H generation (Figure 6). 

GSH has been proposed to be part of the thiol cycling in mammalian cells that may transduce oxidative stress redox signaling into the induction of many genes involved in proliferation, differentiation, and apoptosis [15], Studies with pure chemical systems have confirmed the reduction of V(V) maltol compounds by GSH or ascorbic acid [16], Putative glutathione transferase enzymes that bind vanadium have been isolated from an ascidian that accumulates vanadium in specialized cells to over 350 mM [17],... 

Hence a cycle of reactions was postulated (70) (Figure 3), in which hydrogen peroxide and/or O2 are disposed of via ascorbate and glutathione at the eventual expense of oxidizing NADPH from the electron transport chain. 

Figure 4. Some Interrelationships Between Quinones, Ascorbic acid, Glutathione, and Reducing Power. The cycle of redox events can occur from left to right without intervention of enzymes. Certain enz3rmes can facilitate these reactions 01 - polyphenol oxidase, 02 - peroxidase, R1 - quinone reductase without...

Glutathione and Cu " form several complexes (Petit et al. 1975). Reduction by glutathione triggered a V,iy -bis(2-pyridylmethylene)-l,4-butane-diamine (N,lV,lvr ,lvr )-Cu(II) diperchlorate-supported redox cycle with oxygen yielding H2O2 (Steinkuhler et al. 1991). Whereas reduction by ascorbate was reversible. 

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