Free-Radical Intermediates and Stable Products in the Oxidation of Indole-3-acetic acid

Candeias, Luis P.; Folkes, Lisa K.; Dennis, Madeleine F.; Patel, Kantilal B.; Everett, Steven A.; Stratford, Michael R.L.; Wardman, Peter

doi:10.1021/j100091a031

Cited by 60 publications

(49 citation statements)

References 7 publications

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“…The equipment for spectrophotometry with sub-microsecond resolution used with pulse radiolysis has been described (24).…”

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confidence: 99%

The Reaction of Superoxide Radicals withS-Nitrosoglutathione and the Products of Its Reductive Heterolysis

Ford¹,

Hughes²,

Wardman³

2002

Journal of Biological Chemistry

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Generation of superoxide radicals (0.01-0.1 M s ؊1 ) by radiolysis of aqueous solutions containing S-nitrosoglutathione (45-160 M, pH 3.8 -7.3) resulted in loss of this solute at rates varying with solute concentration, radical generation rate, and pH. The results were quantitatively consistent with the loss being attributed to competition between reaction of superoxide with S-nitrosoglutathione (rate constant 300 ؎ 100 M ؊1 s ؊1 ) and the pH-dependent disproportionation of superoxide/hydroperoxyl. This rate constant is much lower than previous estimates and seven orders of magnitude lower than the rate constants between superoxide and superoxide dismutase or superoxide and nitric oxide. This indicates that interaction between superoxide and Snitrosoglutathione is unlikely to be biologically important, contrary to previous suggestions that reaction could serve to prevent the rapid reaction between superoxide and nitric oxide. Reductive homolysis of Snitrosoglutathione by the carbon dioxide radical anion, a model for biological reductants such as disulfide radical anions, occurred with a rate constant of 7.4 ؋ 10 8 M ؊1 s ؊1 and produced nitric oxide stoichiometrically. Thiyl radicals were not produced, indicating the alternative homolysis route to generate nitroxyl did not occur.

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“…The equipment for spectrophotometry with sub-microsecond resolution used with pulse radiolysis has been described (24).…”

mentioning

confidence: 99%

The Reaction of Superoxide Radicals withS-Nitrosoglutathione and the Products of Its Reductive Heterolysis

Ford¹,

Hughes²,

Wardman³

2002

Journal of Biological Chemistry

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“…The involvement of IAA free radicals (such as the radical cation, the skatolyl radical, etc.) was definitely established [38]. Folkes et al [37,38] identified the skatolyl radical produced by IAA and 2-Me-IAA, as well as 3-methylene-2-oxindole produced by IAA, in combination with HRP, and demonstrated their conjugation with plasmid DNA in vitro.…”

Section: Discussionmentioning

confidence: 99%

Free radical–scavenging activity and DNA damaging potential of auxins IAA and 2‐methyl‐IAA evaluated in human neutrophils by the alkaline comet assay

Salopek‐Sondi

Piljac-Žegarac

Magnus

et al. 2010

J Biochem & Molecular Tox

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Auxins, of which indole-3-acetic acid (IAA) is the most widespread representative, are plant hormones. In addition to plants, IAA also naturally occurs in humans in micromolar concentrations. In the presence of peroxidase, indolic auxins are converted to cytotoxic oxidation products and have thus been proposed for use in gene-directed enzyme/prodrug tumor therapy. Since data on the genotoxicity of IAA and its derivatives are not consistent, here we investigate the early DNA damaging effects (2-h treatment) of the auxins, IAA, and 2-methyl-indole-3-acetic acid (2-Me-IAA) by the alkaline comet assay and compare them with their free radical-scavenging activity measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Human neutrophils are chosen as the test system since they possess inherent peroxidase activity. The results of the comet assay indicate an increase in DNA damage in a dose-dependent manner up to 1.00 mM of both auxins. Generally, IAA applied in the same concentration had greater potential to damage DNA in human neutrophils than did 2-Me-IAA. The genotoxicities of the two examined auxins are negatively correlated with their antioxidant activities, as measured by the DPPH assay; 2-Me-IAA showed a higher antioxidant capacity than did IAA. We assume that differences in the molecular structure of the tested auxins contributed to differences in their metabolism, in particular, with respect to interactions with peroxidases and other oxidative enzymes in neutrophils. However, the exact mechanisms have to be elucidated in future studies.

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“…In our model the time-limiting rate constant for computation is k 6 ) 2.0 × 10 8 M -1 s -1 . 22 For this value of k 6 and zero step-size limit (highest level of integration precision) the calculation of 100 min of numerical data takes about 700 min of computer time, while for k 6 ) 1.0 × 10 6 M -1 s -1 only about 3 min. It was found that k 6 did not influence the result of simulation if k 6 .…”

Section: Computing Resourcesmentioning

confidence: 92%

Detailed Model of the Peroxidase-Catalyzed Oxidation of Indole-3-Acetic Acid at Neutral pH

and

Dunford

1996

J. Phys. Chem.

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A mechanistic model of peroxidase-catalyzed oxidation of indole-3-acetic acid (IAA) at neutral pH has been developed, characterized, and compared with experiments. The model is based on experimental facts showing that IAA is oxidized in the presence of HRP by two pathways: (i) the standard peroxidase cycle, which is accompanied by (ii) a nonenzymatic free radical chain reaction. The peroxidase cycle normally requires the addition of a hydroperoxide, whereas IAA oxidation does not. Therefore, the model includes the enzymatic peroxidase cycle which is initiated by organic hydroperoxide (ROOH) derived from autoxidation of IAA. It also includes a nonenzymatic free radical chain which utilizes oxygen, oxidizes IAA, and recycles ROOH required for the enzymatic cycle. Available experimental values of rate constants were used. Unavailable rate constants were initially estimated analytically using the steady state assumption and then optimized by computer simulation. There is a unique set of rate constants which satisfies the model. The average deviation of simulated kinetic traces from experimental ones was less than 5%. Critical values of the rate constants were determined; for values smaller than the critical values IAA oxidation stops. In the pre-steady state the concentration of ROOH rises exponentially. Thus, a decrease of the initial concentration of ROOH by 3 orders of magnitude gives rise to only a 1 min delay of reaction. For all intermediates except ROOH the steady state was reached in 1 min; for ROOH, 10 min after reaction initiation. More than half of the oxidation of IAA occurs by the chain reaction, a nonenzymatic pathway. The model satisfactorily describes all available experimental kinetic data and predicts some previously unobserved behavior which should stimulate further experiments.

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Free-Radical Intermediates and Stable Products in the Oxidation of Indole-3-acetic acid

Cited by 60 publications

References 7 publications

The Reaction of Superoxide Radicals withS-Nitrosoglutathione and the Products of Its Reductive Heterolysis

The Reaction of Superoxide Radicals withS-Nitrosoglutathione and the Products of Its Reductive Heterolysis

Free radical–scavenging activity and DNA damaging potential of auxins IAA and 2‐methyl‐IAA evaluated in human neutrophils by the alkaline comet assay

Detailed Model of the Peroxidase-Catalyzed Oxidation of Indole-3-Acetic Acid at Neutral pH

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