Dataset Information

Detoxification of superoxide without production of H2O2: antioxidant activity of superoxide reductase complexed with ferrocyanide.

ABSTRACT: The superoxide radical O(2)(-.) is a toxic by-product of oxygen metabolism. Two O(2)(-.) detoxifying enzymes have been described so far, superoxide dismutase and superoxide reductase (SOR), both forming H2O2 as a reaction product. Recently, the SOR active site, a ferrous iron in a [Fe(2+) (N-His)(4) (S-Cys)] pentacoordination, was shown to have the ability to form a complex with the organometallic compound ferrocyanide. Here, we have investigated in detail the reactivity of the SOR-ferrocyanide complex with O(2)(-.) by pulse and gamma-ray radiolysis, infrared, and UV-visible spectroscopies. The complex reacts very efficiently with O(2)(-.). However, the presence of the ferrocyanide adduct markedly modifies the reaction mechanism of SOR, with the formation of transient intermediates different from those observed for SOR alone. A one-electron redox chemistry appears to be carried out by the ferrocyanide moiety of the complex, whereas the SOR iron site remains in the reduced state. Surprisingly, the toxic H2O2 species is no longer the reaction product. Accordingly, in vivo experiments showed that formation of the SOR-ferrocyanide complex increased the antioxidant capabilities of SOR expressed in an Escherichia coli sodA sodB recA mutant strain. Altogether, these data describe an unprecedented O(2)(-.) detoxification activity, catalyzed by the SOR-ferrocyanide complex, which does not conduct to the production of the toxic H2O2 species.

SUBMITTER: Molina-Heredia FP

PROVIDER: S-EPMC1595423 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Detoxification of superoxide without production of H2O2: antioxidant activity of superoxide reductase complexed with ferrocyanide.

Molina-Heredia Fernando P FP Houée-Levin Chantal C Berthomieu Catherine C Touati Danièle D Tremey Emilie E Favaudon Vincent V Adam Virgile V Nivière Vincent V

Proceedings of the National Academy of Sciences of the United States of America 20060925 40

The superoxide radical O(2)(-.) is a toxic by-product of oxygen metabolism. Two O(2)(-.) detoxifying enzymes have been described so far, superoxide dismutase and superoxide reductase (SOR), both forming H2O2 as a reaction product. Recently, the SOR active site, a ferrous iron in a [Fe(2+) (N-His)(4) (S-Cys)] pentacoordination, was shown to have the ability to form a complex with the organometallic compound ferrocyanide. Here, we have investigated in detail the reactivity of the SOR-ferrocyanide ...[more]

PMID: 17001016

Similar Datasets

Project description:ImportanceX-linked adrenoleukodystrophy (ALD) may switch phenotype to the fatal cerebral form (ie, cerebral ALD [cALD]), the cause of which is unknown. Determining differences in antioxidant capacity and superoxide dismutase (SOD) levels between phenotypes may allow for the generation of a clinical biomarker for predicting the onset of cALD, as well as initiating a more timely lifesaving therapy.ObjectiveTo identify variations in the levels of antioxidant capacity and SOD activity between ALD phenotypes in patients with cALD or adrenomyeloneuropathy (AMN), heterozygote female carriers, and healthy controls and, in addition, correlate antioxidant levels with clinical outcome scores to determine a possible predictive value.Design, setting, and participantsSamples of monocytes and blood plasma were prospectively collected from healthy controls, heterozygote female carriers, and patients with AMN or cALD. We are counting each patient as 1 sample in our study. Because adrenoleukodystrophy is an X-linked disease, the affected group populations of cALD and AMN are all male. The heterozygote carriers are all female. The samples were assayed for total antioxidant capacity and SOD activity. The data were collected in an academic hospital setting. Eligibility criteria included patients who received a diagnosis of ALD and heterozygote female carriers, both of which groups were compared with age-matched controls. The prospective samples (n?=?30) were collected between January 2015 to January 2016, and existing samples were collected from tissue storage banks at the Kennedy Krieger Institute (n?=?30). The analyses were performed during the first 3 months of 2016.Main outcome and measuresCommercially available total antioxidant capacity and SOD assays were performed on samples of monocytes and blood plasma and correlated with magnetic resonance imaging severity score.ResultsA reduction in antioxidant capacity was shown between the healthy controls (0.225 mmol trolox equivalent) and heterozygote carriers (0.181 mmol trolox equivalent), and significant reductions were seen between healthy controls and patients with AMN (0.102 mmol trolox equivalent; P?<?.01), as well as healthy controls and patients with cALD (0.042 mmol trolox equivalent; P?<?.01). Superoxide dismutase activity in human blood plasma mirrored these reductions between prospectively collected samples from healthy controls (2.66 units/mg protein) and samples from heterozygote female carriers (1.91 units/mg protein), patients with AMN (1.39 units/mg protein; P?=?.01), and patients with cALD (0.8 units/mg protein; P?<?.01). Further analysis of SOD activity in biobank samples showed significant reductions between patients with AMN (0.89 units/mg protein) and patients with cALD (0.18 units/mg protein) (P?=?.03). Plasma SOD levels from patients with cALD demonstrated an inverse correlation to brain magnetic resonance imaging severity score (R2?=?0.75, P?<?.002). Longitudinal plasma SOD samples from the same patients (n?=?4) showed decreased activity prior to and at the time of cerebral diagnosis over a period of 13 to 42 months (mean period, 24 months).Conclusions and relevancePlasma SOD may serve as a potential biomarker for cerebral disease in ALD following future prospective studies.

Project description:The Panel on Food Additives and Nutrient Sources added to Food (ANS) provided a scientific opinion re-evaluating the safety of sodium ferrocyanide (E 535), potassium ferrocyanide (E 536), and evaluating the safety of calcium ferrocyanide (E 538) as food additives. The Panel considered that adequate exposure and toxicity data were available. Ferrocyanides (E 535-538) are solely authorised in two food categories as salt substitutes. To assess the dietary exposure to ferrocyanides (E 535-538) from their use as food additives, the exposure was calculated based on regulatory maximum level exposure assessment scenario (maximum permitted level (MPL)) and the refined exposure assessment scenario. Dietary exposure to ferrocyanides was calculated based on mean and high levels consumption of salts in both the regulatory maximum level and the refined scenario. In the MPL scenario, the exposure to ferrocyanides (E 535-538) from their use as a food additive was up to 0.009 mg/kg body weight (bw) per day in children and adolescents. In the refined estimated exposure scenario, the exposure was up to 0.003 mg/kg bw per day in children and adolescents. Absorption of ferrocyanides is low and there is no accumulation in human. There is no concern with respect to genotoxicity and carcinogenicity. Reproductive studies were not available, but a no observed adverse effect level (NOAEL) of 1,000 mg sodium ferrocyanide/kg bw per day (highest dose tested) was identified from a prenatal developmental toxicity study. The kidney appeared to be the target organ for ferrocyanides toxicity and 4.4 mg sodium ferrocyanide/kg bw per day was identified as the NOAEL for the renal effects in a chronic (2-year) study in rats. Assuming that the toxicity of this compound is due to the ferrocyanide ion only, the Panel established a group acceptable daily intake (ADI) for sodium, potassium and calcium ferrocyanide of 0.03 mg/kg bw per day expressed as ferrocyanide ion. The Panel concluded that ferrocyanides (E 535-538) are of no safety concern at the current authorised use and use levels.

Dataset Information

Detoxification of superoxide without production of H2O2: antioxidant activity of superoxide reductase complexed with ferrocyanide.

Publications

Detoxification of superoxide without production of H2O2: antioxidant activity of superoxide reductase complexed with ferrocyanide.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure