Ascorbate radical

The platinum(II) catalyzed reduction of civ,civ,/rart.v-diaminedihalodihydroxoplatinum(IV) complexes by ascorbate has been reported to proceed via a long-lived platinum(IV)-ascorbate radical.518 Ascorbate reduction of complexes with halides in the axial sites has been reported to proceed via reductive attack on one of these halides.519 This group also showed that reduction by A sc2 occurred seven orders of magnitude more rapidly than reduction by I IAsc and that H2Asc is unreactive.519 Reduction by thiols and methionine is strongly dependent on pH because of a similar variation in reactivity of the protonated and unprotonated forms of the reductants.505,514... 

Therefore, depending on their structures, flavonoids may reduce the ascorbate radical or oxidize ascorbate, exhibiting antioxidant or prooxidant properties in the systems containing flavonoids and ascorbate together. 

Electron transfer accompanied by release of the oxidized ascorbate, the ascorbate radical, HA ... 

Tyrosinase is both an oxidase and a hydroxylase. Some other copper enzymes have only a hydroxylase function. One of the best understood of these is the peptidylglycine a-hydroxylating monoxygenase, which catalyzes the first step of the reaction of Eq. 10-11. The enzyme is a colorless two-copper protein but the copper atoms are 1.1 nm apart and do not form a binuclear center.570 Ascorbate is an essential cosubstrate, with two molecules being oxidized to the semidehydro-ascorbate radical as both coppers are reduced to Cu(I). A ternary complex of reduced enzyme, peptide, and 02 is formed and reacts to give the hydroxylated product.570 A related two-copper enzyme is dopamine (J-monooxygenase, which utilizes 02 and ascorbate to hydroxylate dopamine to noradrenaline (Chapter 25).571/572 These and other types of hydroxylases are compared in Chapter 18. 

Two ascorbate radicals can react with each other in a disproportionation reaction to give ascorbate plus dehydroascorbate. However, most cells can reduce the radicals more directly. In many plants this is accomplished by NADH + H+ using a flavoprotein monodehydroascorbate reductase.0 Animal cells may also utilize NADH or may reduce dehydroascorbate with reduced glutathione.CC/ff Plant cells also contain a very active blue copper ascorbate oxidase (Chapter 16, Section D,5), which catalyzes the opposite reaction, formation of dehydroascorbate. A heme ascorbate oxidase has been purified from a fungus. 11 1 Action of these enzymes initiates an oxidative degradation of ascorbate, perhaps through the pathway of Fig. 20-2. 

The bimolecular decay of the ascorbate radical is much more complex than shown in the overall reaction (86). In fact, it is in equilibrium with a dimer [equilibrium (88), K 103 dm3 mol-1, kieverse 105 s"1] which either may react with a proton [reaction (89), k = 1010 dm3 mol-1 s"1] or with water [reaction (90), k 40 s"1] (Bielski et al. 1981). 

Biaglow JE, Kachur AV (1997) The generation of hydroxyl radicals in the reaction of molecular oxygen with polyphosphate complexes of ferrous ion. Radiat Res 148 181-187 Biaglow JE, Field KD, Manevich Y, Tuttle S, Kachur A, Uckun F (1996) Role of guanosine triphosphate in ferric ion-linked Fenton chemistry. Radiat Res 145 554-562 Bielski BHJ (1991) Studies of hypervalent iron. Free Radical Res Commun 12/13 469-477 Bielski BHJ, Allen AO, Schwarz HA (1981) Mechanism of disproportionation of ascorbate radicals. J Am Chem Soc 103 3516-3518... 

Buettner GR (1988) In the absence of catalytic metals ascorbate does not autoxidize at pH 7 ascorbate as a test for catalytic metals. J Biochem Biophys Methods 16 27-40 Buettner GR, Jurkiewicz BA (1995) Ascorbate radical a valuable marker of oxidative stress. In Favier AE, Cadet J, Kalyanaraman B, Fontecave M, Piere JL (eds) Analysis of free radicals in biological systems. Birkhauser, Basel, pp 145-164... 

The ascorbate radical is one of the radicals that do not react readily with 02, but it reacts with 02 ". The product of this reaction is not yet known. There are other radicals that have similar properties such as phenoxyl-type radicals. A prominent member of this group is the vitamin E radical. In the phenoxyl radical series, addition as well as ET have been discussed (Jonsson et al. 1993 d Alessandro et al. 2000). The reaction of the tyrosyl radical with 02 is an example showing that addition is the main route despite of its relatively high redox potential [reactions (97)—(99) only one pathway is shown Jin et al. 1993],... 

In all of these reactions, thiyl radicals are formed which are still quite reactive in many aspects (Chap. 7.4). In a cellular environment, they will have to be inactivated. Originally, 02 was thought to be the radical sink according to reactions (78) and (79), but more recent kinetic evidence has shown that it may be the ascorbate radical [reaction (80)] (Wardman 1995, 1998). 

FIGURE 29.1 Pathways of the chain-breaking action of vitamin E in lipid peroxidation and its subsequent regeneration. LOOH lipid hydroperoxide, LOO lipid peroxyl radical, vitamin C ascorbate radical (semi-dehydroascorbate), vitamin E a-tocopheroxyl radical. The lipid peroxyl radical is reduced to lipid hydroperoxide by tocopherol. The resulting tocopheroxyl radical can be re-reduced by ascorbate. The thus formed ascorbate radical can be reduced to ascorbate by the NADH-dependent semidehydroascorbate reductase. 

Delocalisation onto oxygen stabilizes radicals considerably. An important example is the ascorbate radical (Scheme 1.3) formed by electron-loss from the ascorbate anion, or electron-capture by dehydroascorbate. This is remarkably stable, and is characterized by an ESR doublet (1.7 G) which is quite distinctive. Because of the high sensitivity of ESR spectroscopy, and the fact that opaque samples can be used, ascorbate radical intermediates have been widely studied (Liu et al., 1988a). The most probable structure is shown in Scheme 1.3 but this is still a matter of some controversy (Liu et al., 1988a). A key factor in the formation of ascorbate radicals is that ascorbate anions... 

Although nitroxide radicals do not seem to exist in naturally biological systems, they are relatively non-toxic, and survive as such for considerable periods after administration. This property makes them important as spin-labels in biological systems, ESR spectroscopy being an ideal technique for studying their behaviour. However, in these studies their radical nature is not significant chemically it is the presence of an unpaired electron, and the remarkable stability of these species that is utilized. However, nitroxides can act as electron donors and acceptors, and we compare them here with ascorbate radicals (Section 1.4). 

This contrasts with the ascorbate system in which two ascorbate radicals give ascorbate + dehydroascorbate. 

Asada, K., Miyake, C., Ogawa, K., and Hossain, M. A., 1996, Microcompartmentation of ascorbate peroxidase and regeneration of ascorbate from ascorbate radical its dual role in chloroplasts, in Plant Peroxidases Biochemistry and Physiology (C. Obinger, U. Burner, R. Ebermann, C. Penel, and H. Greppin, eds.). University of Geneva, pp. 163nl67. 

A further example for the ad -el mechanism is the reaction of OH with the strong reductant ascorbic acid. This reaction, which leads to the oxidation of ascorbic acid to yield the ascorbate radical, proceeds by addtion to the olefinic bond of the reductone function followed by elimination of OH Abe, A. Okada, S. Nakao, R. Horii, T. Inoue, H. Taniguchi, S. Yamabe, S. J. Chem. Soc. Perkin Trans. 2 1992, 2221. 

The term vtiamin C refers to ascorbic acid (the fully reduced form of the vitamin) and to dchydroascorbic acid- Removal of one electron from ascorbic acid yields semidehydroascorbic acid (ascorbate radical). This form of the vitamin is a free radical it contains an unpaired electron- The structures of free radicals are written with large dots. The removal of a second electron yields dehydroascorbic acid. Conversion of ascorbate to dehydroascorbate, via the removal of two electrons, can occur under two conditions (1) with use of ascorbic add by ascorbate-dependent enzymes and (2) with the spontaneous reaction of ascorbate with oxygen. Semidehydroascorbate is an intermediate in this conversion palhway... 

Figure 13.10. Schematic representation of the oxide dissolution processes [exemplified for Fe(III) (hydr)oxides] by acids (H ions), ligands (example oxalate), and reductants (example ascorbate). In each case a surface complex (proton complex, oxalato and ascorbato surface complex) is formed, which influences the bonds of the central Fe ions to O and OH on the surface of the crystalline lattice, in such a way that a slow detachment of a Fe(III) aquo or a ligand complex [in case of reduction an Fe(ll) complex] becomes possible. In each case the original surface structure is reconstituted, so that the dissolution continues (steady-state condition). In the redox reaction with Fe(III), the ascorbate is oxidized to the ascorbate radical A . The principle of proton-promoted and ligand-promoted dissolution is also valid for the dissolution (weathering) of Al-silicate minerals. The structural formulas given are schematic and simplified they should indicate that Fe(III) in the solid phase can be bridged by O and OH.

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