Deoxyribose Peroxidation

Oxidants such as hydroxyl radical or peroxynitrite also react with the 2 -deoxyribose scaffold of DNA. Each hydrogen on the 2 -deoxyribose ring is subject to free radical-mediated abstraction and subsequent diffusion-limited reaction with molecular oxygen. Each site of peroxidation leads to a separate and overlapping array of products. Following hydrogen abstraction on 2 -deoxyribose by reactive oxygen 

4-oxo-2-nonenal, 4-hydroxy-2-nonenal, 4,5-epoxy-2-decenal, and 9,12-dioxo-10-dodecenoic acid. (Inset) a,P-Unsaturated aldehydes acrolein and crotonaldehyde are also products of lipid peroxidation. 

Chemistry at the 4 -position of 2 -deoxyribose has been extensively studied due to the availability of reagents producing radical formation at this site (bleomycin, calicheamicin, peroxynitrite, and Fe2+-EDTA) [25-28]. 4 -Free radical formation 

The bifunctional nature of many lipid peroxidation products provides two reactive centers. Addition reactions to pyrimidines and purines often confer exocyclic 

MDA is an abundant product of lipid peroxidation and one of the first products identified to arise from the oxidation of lipids [31-33]. MDA is a bifunctional electrophile with pH-dependent reactivity, which exists as the P-hydroxyacrolein tautomer in polar solvents and forms an enolate at physiological pH (pJC, = 4.46) [34, 35]. The structurally related base propenals are P-substituted acroleins that are similar to P-hydroxyacrolein in their reactivity with nucleophiles, but they are not ionizable at physiological pH. 

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In 1977, Kellogg and Fridovich [28] showed that superoxide produced by the XO-acetaldehyde system initiated the oxidation of liposomes and hemolysis of erythrocytes. Lipid peroxidation was inhibited by SOD and catalase but not the hydroxyl radical scavenger mannitol. Gutteridge et al. [29] showed that the superoxide-generating system (aldehyde-XO) oxidized lipid micelles and decomposed deoxyribose. Superoxide and iron ions are apparently involved in the NADPH-dependent lipid peroxidation in human placental mitochondria [30], Ohyashiki and Nunomura [31] have found that the ferric ion-dependent lipid peroxidation of phospholipid liposomes was enhanced under acidic conditions (from pH 7.4 to 5.5). This reaction was inhibited by SOD, catalase, and hydroxyl radical scavengers. Ohyashiki and Nunomura suggested that superoxide, hydrogen peroxide, and hydroxyl radicals participate in the initiation of liposome oxidation. It has also been shown [32] that SOD inhibited the chain oxidation of methyl linoleate (but not methyl oleate) in phosphate buffer. 

Malonaldehyde, a three-carbon dialdehyde (OHC- -CHO), is produced during lipid peroxidation by the oxidative decomposition of arachi donic and other unsaturated fatty acids. Malonaldehyde is present in a number of food products and its concentration is increased by irradiation of cellular amino acids, carbohydrates, deoxyribose, and DNA. Recent surveys (31-32) have confirmed the presence of malonaldehyde in supermarket samples of meat, poultry, and fish,... 

Sugden KD, Wetterhahn KE. 1997. Direct and hydrogen peroxide-induced chromium(V) oxidation of deoxyribose in single-stranded and double-stranded calf thymus DNA. Chem Res Toxicol 10 1397-1406. 

The salvage pathway does not involve the formation of new heterocyclic bases but permits variation according to demand of the state of the base (B), i.e. whether at the nucleoside (N), or nucleoside mono- (NMP), di- (NDP) or tri- (NTP) phosphate level. The major enzymes and routes available (Scheme 158) all operate with either ribose or 2-deoxyribose derivatives except for the phosphoribosyl transferases. Several enzymes involved in the biosynthesis of purine nucleotides or in interconversion reactions, e.g. adenosine deaminase, have been assayed using a method which is based on the formation of hydrogen peroxide with xanthine oxidase as a coupling enzyme (81CPB426). 

The effects of berbamine, oxyacanthine, and berberine on 5-lipoxygenase lipid peroxidation in phospholipid liposomes induced by 2,2 -azo-(bis-2-amidinopropane)(AAPH), deoxyribose degradation, and their reactivities against the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) were studied. None of the alkaloids showed any appreciable effects in the inhibition of 5-lipoxygenase. Reactivity against DPPH increased in the following order berberine < oxyacanthine < berbamine. Pro-oxidant effects of the alkaloids were excluded, since deoxyribose degradation was not influenced as determined by the release of malondialdehyde [200],... 

In the case of copper complexes, the chemistry is less well understood. High valent copper-oxo species are not likely to be formed, consequently copper-hydroperoxo or copper-hydroxo species are usually proposed as active species in DNA oxidation. These species are thus more susceptible to homo-lytic cleavage of the peroxide or the metal-hydroxo bond and consequently, to 1-electron oxidation mechanism. However, the labeling of the product of deoxyribose oxidation at Cl by Cu(l,10-phenanthroline)2 clearly demonstrated that these complexes can mediate a 2-electron oxidation mechanism of DNA damage since the oxygen atom incorporated in DNA originates from H2O. 

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