Superoxide‐dependent production of hydroxyl radical catalyzed by iron—EDTA complex

McCord, Joe M.; Day, Eugene D.

doi:10.1016/0014-5793(78)80116-1

Cited by 832 publications

(271 citation statements)

References 15 publications

(2 reference statements)

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“…NADH and NADPH, however, did make a small contribution to OH' production, but the mechanism involved O2-r Autoxidation of the NADH (or NADPH) catalysed by the iron-EDTA is the most probable source of the 02---It has been suggested that the reaction of 02-with chelated iron and H202 may be an important source of OH' in biological systems, and that one of the prime functions of superoxide dismutase may be to prevent such reactions (Cohen, 1977;McCord & Day, 1978 (McCord & Day, 1978).…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism for production was originally postulated to be the Haber-Weiss reaction (Fridovich, 1975): 02-+H202 OH-0+02+OH-but kinetic data have subsequently shown that this is too slow to be of significance (Halliwell, 1976;McClune & Fee, 1976;Czapski & Ilan, 1978). However, this reaction occurs more rapidly when catalysed by iron-EDTA, and a mechanism of this type has been suggested as an alternative (Cohen, 1977;McCord & Day, 1978). EDTA-complexed Fe2+ reacts with H202 by a Fenton-type reaction (2), and the role of the O2-is to reduce the ferric complex thus formed (3), the net result being reaction (1).…”

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confidence: 99%

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Comparison of superoxide with other reducing agents in the biological production of hydroxyl radicals

Winterbourn¹

1979

Biochemical Journal

263

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Comparison of superoxide with other reducing agents in the biological production of hydroxyl radicals

Winterbourn¹

1979

Biochemical Journal

263

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“…Several workers have investigated the effect of EDTA on irondependent hydroxyl radical-generating systems, but results have ranged from stimulation throughnoeffect toinhibition [4][5][6][7]10,13,14,17,18]. Table 2 provides some indication of the reasons for such variability.…”

Section: L Damage To Deoxytibose By Iron (Ii) Saltsmentioning

confidence: 99%

“…A mixture of xanthine and xanthine oxidase generates O;-and H202 [ 151 and, in the presence of I.tM levels of iron salts, these can react together to form OH' radicals [6,7]. All chemical reagents and biological fluids are contaminated with iron salts at concentrations sufficient to produce OH' [5,7,17,18].…”

Section: Damage To Deoxyribose By a Oi--generating Systemmentioning

confidence: 99%

Formation of a thiobarbituric‐acid‐reactive substance from deoxyribose in the presence of iron salts

1981

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“…That reductant has not been identified. Superoxide itself is capable of reducing free iron and functions in that capacity in some in vitro Fenton systems (8,9,18). However, the intracellular concentration of superoxide is so low (ϳ10 Ϫ10 M) (19,20), and its reduction of bound iron so slow (ϳ10 5 M Ϫ1 s Ϫ1 ) (21), that the predicted half-time for this reaction in vivo is Ͼ10 h, far too long to be physiologically relevant.…”

mentioning

confidence: 99%

Reduced Flavins Promote Oxidative DNA Damage in Non-respiringEscherichia coli by Delivering Electrons to Intracellular Free Iron

Woodmansee

Imlay

2002

Journal of Biological Chemistry

130

163

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When cells are exposed to external H 2 O 2 , the H 2 O 2 rapidly diffuses inside and oxidizes ferrous iron, thereby forming hydroxyl radicals that damage DNA. Thus the process of oxidative DNA damage requires only H 2 O 2 , free iron, and an as-yet unidentified electron donor that reduces ferric iron to the ferrous state. Previous work showed that H 2 O 2 kills Escherichia coli especially rapidly when respiration is inhibited either by cyanide or by genetic defects in respiratory enzymes. In this study we established that these respiratory blocks accelerate the rate of DNA damage. The respiratory blocks did not substantially affect the amounts of intracellular free iron or H 2 O 2 , indicating that that they accelerated damage because they increased the availability of the electron donor. The goal of this work was to identify that donor. As expected, the respiratory inhibitors caused a large increase in the amount of intracellular NADH. However, NADH itself was a poor reductant of free iron in vitro. This suggests that in non-respiring cells electrons are transferred from NADH to another carrier that directly reduces the iron. Genetic manipulations of the amounts of intracellular glutathione, NADPH, ␣-ketoacids, ferredoxin, and thioredoxin indicated that none of these was the direct electron donor. However, cells were protected from cyanide-stimulated DNA damage if they lacked flavin reductase, an enzyme that transfers electrons from NADH to free FAD. The K m value of this enzyme for NADH is much higher than the usual intracellular NADH concentration, which explains why its flux increased when NADH levels rose during respiratory inhibition. Flavins that were reduced by purified flavin reductase rapidly transferred electrons to free iron and drove a DNA-damaging Fenton system in vitro. Thus the rate of oxidative DNA damage can be limited by the rate at which electron donors reduce free iron, and reduced flavins become the predominant donors in E. coli when respiration is blocked. It remains unclear whether flavins or other reductants drive Fenton chemistry in respiring cells.

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Superoxide‐dependent production of hydroxyl radical catalyzed by iron—EDTA complex

Cited by 832 publications

References 15 publications

Comparison of superoxide with other reducing agents in the biological production of hydroxyl radicals

Comparison of superoxide with other reducing agents in the biological production of hydroxyl radicals

Formation of a thiobarbituric‐acid‐reactive substance from deoxyribose in the presence of iron salts

Reduced Flavins Promote Oxidative DNA Damage in Non-respiringEscherichia coli by Delivering Electrons to Intracellular Free Iron

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