Copper oxide Glutathion

Copper reduces glutathione, which is necessary for normal cell viability. The amino acid transferases are inhibited in the presence of excess copper lipid peroxidation also occurs. Copper combines with thiol groups, which reduces the oxidation state II to I in copper and oxidizes the thiol groups to disulfides, especially in the cell membrane. 

Kachur, A., Koch, C., and Biaglow, J., Mechanism of copper-catalyzed oxidation of glutathione, Free Radic Res, 28 (3), 259-269, 1998. 

Thomas and Jackson [329] have shown that ebselen inhibited copper-initiated LDL oxidation in the presence of glutathione. Noguchi et al. [330] showed that the inhibitory effect of ebselen on copper-initiated LDL was also observed without glutathione, while in the case of radical-initiated LDL oxidation ebselen was inactive. However, it is possible that ebselen may inhibit both copper- and peroxyl radical-initiated LDL oxidation although in the latter case the inhibitory effect of ebselen depends on the size of peroxyl radical flux [331]. The inhibitory effect of ebselen on LDL oxidation also depends on its ability to reduce LDL hydroperoxides. 

Metallothioneins (MT) are unique 7-kDa proteins containing 20 cysteine molecules bounded to seven zinc atoms, which form two clusters with bridging or terminal cysteine thiolates. A main function of MT is to serve as a source for the distribution of zinc in cells, and this function is connected with the MT redox activity, which is responsible for the regulation of binding and release of zinc. It has been shown that the release of zinc is stimulated by MT oxidation in the reaction with glutathione disulfide or other biological disulfides [334]. MT redox properties led to a suggestion that MT may possesses antioxidant activity. The mechanism of MT antioxidant activity is of a special interest in connection with the possible antioxidant effects of zinc. (Zinc can be substituted in MT by some other metals such as copper or cadmium, but Ca MT and Cu MT exhibit manly prooxidant activity.)... 

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. 

In its biochemical functions, ascorbic acid acts as a regulator in tissue respiration and tends to serve as an antioxidant in vitro by reducing oxidizing chemicals. The effectiveness of ascorbic acid as an antioxidant when added to various processed food products, such as meats, is described in entry on Antioxidants. In plant tissues, the related glutathione system of oxidation and reduction is fairly widely distributed and there is evidence that election transfer reactions involving ascorbic acid are characteristic of animal systems. Peroxidase systems also may involve reactions with ascorbic acid In plants, either of two copper-protein enzymes are commonly involved in the oxidation of ascorbic acid. 

Ghyczy M, Boros M (2001) Electrophilic methyl groups present in the diet ameliorate pathological states induced by reductive and oxidative stress a hypothesis. Br J Nutr 85 409-414 Gilbert BC, Silvester S (1997) EPR studies of the role of copper in bio-organic free radical reactions. Copper-catalyzed oxidations of thiols with peroxides, especially those involving glutathione. Nukleonika 42 307-322... 

De Vos et al. (1989) suggest that the copper-induced damage to the permeability barrier in roots of Silene cucubalus is caused by a direct metal action on both membrane lipids and thiols. They propose that the first damaging effects of copper ions is the oxidation and cross-linking of membrane protein sulphydryls. However, they also adjudge an important role to the copper induced membrane lipid peroxidation, possibly due to direct free radical formation in the membrane this effect could be enhanced by a depletion of thiols such as glutathione which results in a concomitant decrease of the cellular defence system against free radicals. 

Formation of zero-valent copper clusters with glutathione has been studied anaerobically. The ligand has been reported to provide a snbstantial degree of surface passivation. Rednction of a Cu(II)-GSH complex prodnced nanoparticles with a plasmon resonance band at 363 nm. These nanoparticles possessed a diameter of 9.7 4.3nm as demonstrated by TEM analysis. Under aerobic conditions, the nanoparticles oxidatively degrade as evinced by the loss of the plasmon absorption band over time. 

Recently, several studies have found that black tea and green tea offered protection against oxidative damage to red blood cells induced by a variety of inducers, such as hydrogen peroxide, primaquine, 2,2 -azo-fc (2-amidinopropane) dihydrochloride (AAPH), phenylhydrazine, copper-ascorbic acid, and the xanthine/xanthine oxidase system. Recently, we found that oral feeding of green tea leaves to rats resulted in enhanced superoxide dismutase (SOD) activity in serum and catalase activity in liver and an increased concentration of glutathione in the liver. ... 

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