Intramolecular Transformation Reaction of the Glutathione Thiyl Radical into a Non-sulphur-centred Radical: A Pulse-radiolysis and EPR Study

Grierson, Lebert; Hildenbrand, Knut; Bothe, Eberhard

doi:10.1080/09553009214552111

Cited by 73 publications

(46 citation statements)

References 27 publications

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“…This species becomes much more obvious when SOD is included in the reaction mixture. The source of this radical is unknown, but there is a report of glutathione thiyl radical spontaneously transforming into a carbon-centered radical (26). It may be that we are observing the same type of rearrangement in dihydrolipoic acid.…”

Section: Resultsmentioning

confidence: 97%

Sulfur-centered Radical Formation from the Antioxidant Dihydrolipoic Acid

Mottley¹,

Mason²

2001

Journal of Biological Chemistry

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Lipoic acid and its reduced form, dihydrolipoic acid, are thought to be strong antioxidants. There are also reports of dihydrolipoic acid acting as a pro-oxidant under certain circumstances. This article reports the direct observation by ESR spectrometry of the disulfide radical anion and the spin trapping of the primary thiyl radical formed from the oxidation of dihydrolipoic acid through thiol pumping with phenol and horseradish peroxidase. The disulfide radical anion reacts rapidly with oxygen to form the reactive radical superoxide, which is also trapped. The radical species formed show a potential for pro-oxidant activity of this compound. Although antioxidants, in general, have been shown to have pro-oxidant potential, the pro-oxidant chemistry of dihydrolipoic acid has not been well characterized.There has been much recent interest in ␣-lipoic acid as a powerful antioxidant in animals based primarily on observations that it or its reduced form, dihydrolipoic acid, scavenges hydroxyl radical (1-3), superoxide (2), singlet oxygen (4, 5), and hypochlorous acid (1, 6, 7). In addition, lipoic acid recycles the well known antioxidants ascorbate, glutathione, and vitamin E by reducing their radical form back to the parent compound (8 -11). The antioxidant properties have been reviewed in several papers (12, 13) and so will not be extensively discussed here. Lipoic acid is used to treat toxicities in which free radicalinduced peroxidation of membrane phospholipids is thought to be important (14 -16) and, with vitamin E, has been shown to improve cardiac function after ischemia in rats (17).On the other hand, there are a limited number of reports describing potential pro-oxidant effects of dihydrolipoic acid such as releasing iron from ferritin (18), reducing Fe 3ϩ to Fe 2ϩ in microsomes (19), accelerating deoxyribose degradation by FeCl 3 -EDTA and H 2 O 2 (1), peroxidation of oxidized brain phospholipid liposomes in the presence of Fe 3ϩ (1), accelerating ␣ 1 -antiproteinase inactivation (1), and accelerating the loss of creatine kinase activity in plasma exposed to gas-phase cigarette smoke (1).The oxidation of thiols involves quite complicated chemistry and a number of free radical species (20 -28), each of which has the potential for causing damage in a biological system. It is possible to initiate this oxidation through a process referred to as "thiol pumping" in which a compound, typically a phenol, is metabolized to a reactive free radical by one of a number of peroxidase enzymes, and the radicals so formed are reduced by a thiol, forming a very reactive thiyl radical (29 -36). Thiyl and superoxide radicals produced in this manner from glutathione have been observed by spin trapping (29,31,33,34) while the glutathione disulfide radical anion has been observed directly with ESR (30).Investigators have, until now, been unable to detect sulfurcentered radicals from dihydrolipoic acid in such a system (31, 33) although superoxide production and cycling of the phenoxyl radical back to phenol indicate that the d...

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Section: Resultsmentioning

confidence: 97%

Sulfur-centered Radical Formation from the Antioxidant Dihydrolipoic Acid

Mottley¹,

Mason²

2001

Journal of Biological Chemistry

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“…For example, thiyl radicals can decay via intramolecular rearrangement reaction by which the hydrogen of CH 2 group at the a-position transfers to sulfur atom leading to the formation of carbon-centered radicals. [56,57] So, we speculate that more than 30-40% damaged GSH molecules were attacked by hydroxyl radical and hydrogen atom via reaction (1) and (3) to form GS , which were further dimerized to form GSSG.…”

Section: Mechanismsmentioning

confidence: 98%

Assessment of Damage of Glutathione by Glow Discharge Plasma at the Gas–Solution Interface through Raman Spectroscopy

Zhang

Huang

2012

Plasma Processes & Polymers

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Although non‐thermal discharge plasma is more and more applied in biological field, the molecular mechanisms of plasma acting on biomolecules are still unclear, which are indispensable for understanding the plasma‐induced biological effects. In this work, discharge plasma at the gas–solution interface was employed to irradiate on reduced glutathione (GSH), the most abundant low molecular weight thiol‐containing antioxidant in cells. Through Raman spectroscopy, both the irreversible damage and reversible conversion of GSH to oxidized glutathione (GSSG) were monitored in a non‐destructive fashion, so that the reaction kinetic processes through multi‐pathways could be evaluated quickly and quantitatively. Based on the experimental data, the reaction mechanism was discussed. magnified image

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“…ularly from an a-carbon center to the S-centered GS' radical (10). Because S-H bonds are usually more labile than C-H bonds and hydrogen transfer normally goes from S-H to carbon-centered radicals (8, 1 l), viz:…”

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confidence: 99%

Oxidative damage to the glycyl α-carbon site in proteins: an ab initio study of the C—H bond dissociation energy and the reduction potential of the C-centered radical

Armstrong¹,

Yu²,

Rauk³

1996

Can. J. Chem.

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The C—H bond dissociation energies (DC—H) of a series of model glycyl proteins were derived from selected isodesmic reactions based on high level ab initio calculations. At 298 K, the recommended values of DC—H, in kJ mol−1 are: NH2CH2CHO, 308; NH2CH2C(O)NH2, 336; HC(O)NHCH2CHO, 331; HC(O)NHCH2C(O)NH2, 350; CH3C(O)NHCH2C(O)NH2, 347; HC(O)NHCH2C(O)NHCH3, 349; and CH3C(O)NHCH2C(O)NHCH3, 346. The average of the last four values, 348 kJ mol−1, is the predicted bond dissociation energy of the α-C—H bond of a glycyl protein. The reduction potential in aqueous medium at 298 K and pH 7 for the process, R• + H+ + e− = RH, where R• = XNHCH•C(O)Y and X and Y represent extension of the protein chain, is E0′ 0.8 V. This result suggests that the α-C—H bond of a glycyl protein is susceptible to attack by RS•, ROO•, tyrosyl, and OH• radicals, whose reduction potentials for the analogous process are higher. The present study has established that the molecule HC(O)NHCHRC(O)NH2 (R = an amino acid side chain) serves as an accurate model for the α-C environment of an amino acid residue in a protein, and that a reliable DC—H value for the α-C—H bond may be obtained from calculations on this model at the B3LYP/6-31G(D) level of theory in conjunction with an isodesmic reaction using neutral glycine as reference. Key words: glycine, peptide, amino acid, bond energy, radicals, ab initio, computation.

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Intramolecular Transformation Reaction of the Glutathione Thiyl Radical into a Non-sulphur-centred Radical: A Pulse-radiolysis and EPR Study

Cited by 73 publications

References 27 publications

Sulfur-centered Radical Formation from the Antioxidant Dihydrolipoic Acid

Sulfur-centered Radical Formation from the Antioxidant Dihydrolipoic Acid

Assessment of Damage of Glutathione by Glow Discharge Plasma at the Gas–Solution Interface through Raman Spectroscopy

Oxidative damage to the glycyl α-carbon site in proteins: an ab initio study of the C—H bond dissociation energy and the reduction potential of the C-centered radical

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