Oxidation of melatonin by oxoferryl hemoglobin: A mechanistic study

Tesoriere, Luisa; Avellone, Giuseppe; Ceraulo̊, Leopoldo; D’Arpa, Daniele; Allegra, Mario; Livrea, Maria Antonia

doi:10.1080/10715760100301161

Cited by 33 publications

(39 citation statements)

References 36 publications

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“…To monitor changes in the absorption spectrum of melatonin mediated by the MPO/H 2 O 2 system, the spectral properties of both melatonin and the resulting metabolite were investigated. The spectrum of the resulting metabolite was similar to that of N 1 -acetyl-N 2 -formyl-5-methoxykynuramine (AFMK) as described recently (8,10,15). In contrast to melatonin, AFMK shows substantial absorbance in the range of 330 -350 nm (not shown), which was the reason to follow the kinetics of melatonin oxidation at 340 nm.…”

Section: Reduction Of Compound II By Melatoninsupporting

confidence: 72%

“…Systematic studies have provided evidence that melatonin can act as an effective radical scavenger, thus protecting organisms from oxygen radical damage (3). Recent evidence has been provided that melatonin is a good electron donor in the reduction of hemoglobin oxoferryl species (10). This led us to hypothesize that it may also function as a substrate for peroxidases.…”

Section: Resultsmentioning

confidence: 97%

“…Since recent evidence has shown that melatonin can reduce hypervalent iron species similar to those involved in the catalytic cycle of MPO (10), in the present paper we have investigated the reaction of melatonin with both redox intermediates of MPO by using multimixing stopped-flow spectroscopy, in order to clarify if myeloperoxidase-mediated melatonin oxidation could be of physiological relevance.…”

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confidence: 99%

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Mechanism of Reaction of Melatonin with Human Myeloperoxidase

Allegra¹,

Furtmüller²,

Regelsberger³

et al. 2001

Biochemical and Biophysical Research Communications

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Section: Reduction Of Compound II By Melatoninsupporting

confidence: 72%

Section: Resultsmentioning

confidence: 97%

mentioning

confidence: 99%

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Mechanism of Reaction of Melatonin with Human Myeloperoxidase

Allegra¹,

Furtmüller²,

Regelsberger³

et al. 2001

Biochemical and Biophysical Research Communications

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“…Tesoriere et al [64] recently observed that melatonin undergoes two one-electron donation steps to reduce the reactive oxoferryl hemoglobin (oxoferryl-Hb) molecule. Fig.…”

Section: Electron Donationmentioning

confidence: 98%

“…(5). The proposed two one electron transfer steps during melatonin's interaction with reactive oxoferrylhemoglobin [64]. MTL = melatonin, MLT .…”

Section: Additionmentioning

confidence: 99%

Chemical and Physical Properties and Potential Mechanisms: Melatonin as a Broad Spectrum Antioxidant and Free Radical Scavenger

Tan

Reíter

Manchester

et al. 2002

CTMC

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910

706

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Melatonin was found to be a potent free radical scavenger in 1993. Since then over 800 publications have directly or indirectly confirmed this observation. Melatonin scavenges a variety of reactive oxygen and nitrogen species including hydroxyl radical, hydrogen peroxide, singlet oxygen, nitric oxide and peroxynitrite anion. Based on the analyses of structure-activity relationships, the indole moiety of the melatonin molecule is the reactive center of interaction with oxidants due to its high resonance stability and very low activation energy barrier towards the free radical reactions. However, the methoxy and amide side chains also contribute significantly to melatonin's antioxidant capacity. The N-C=O structure in the C3 amide side chain is the functional group. The carbonyl group in the structure of N-C=O is key for melatonin to scavenge the second reactive species and the nitrogen in the N-C=O structure is necessary for melatonin to form the new five membered ring after melatonin's interaction with a reactive species. The methoxy group in C5 appears to keep melatonin from exhibiting prooxidative activity. If the methoxy group is replaced by a hydroxyl group, under some in vitro conditions, the antioxidant capacity of this molecule may be enhanced. However, the cost of this change are decreased lipophility and increased prooxidative potential. Therefore, in in vivo studies the antioxidant efficacy of melatonin appears to be superior to its hydroxylated counterpart. The mechanisms of melatonin's interaction with reactive species probably involves donation of an electron to form the melatoninyl cation radical or through an radical addition at the site C3. Other possibilities include hydrogen donation from the nitrogen atom or substitution at position C2, C4 and C7 and nitrosation. Melatonin also has the ability to repair damaged biomolecules as shown by the fact that it converts the guanosine radical to guanosine by electron transfer. Unlike the classical antioxidants, melatonin is devoid of prooxidative activity and all known intermediates generated by the interaction of melatonin with reactive species are also free radical scavengers. This phenomenon is defined as the free radical scavenging cascade reaction of the melatonin family. Due to this cascade, one melatonin molecule has the potential to scavenge up to 4 or more reactive species. This makes melatonin very effective as an antioxidant. Under in vivo conditions, melatonin is often several times more potent than vitamin C and E in protecting tissues from oxidative injury when compared at an equivalent dosage (micromol/kg). Future research in the field of melatonin as a free radical scavenger might be focused on: 1), signal transduction and antioxidant enzyme gene expression induced by melatonin and its metabolites, 2), melatonin levels in tissues and in cells, 3), melatonin structure modifications, 4), melatonin and its metabolites in plants and, 5), clinical trials using melatonin to treat free radical related diseases such as Alzheimer's, Parkinson's, s...

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