title: Iron chelation and redox chemistry of anthranilic acid and 3-hydroxyanthranilic acid: A comparison of two structurally related kynurenine pathway metabolites to obtain improved insights into their potential role in neurological disease development.
abstract: Anthranilic acid (ANA) and 3-hydroxyanthranilic acid (3-HANA) are kynurenine pathway intermediates of the tryptophan metabolism. A hitherto unemployed method combination, differential pulse voltammetry, mass spectrometry (nano-ESI-MS), deoxyribose degradation and iron(II) autoxidation assays has been employed for studying of their redox chemistry and their interactions with iron(II) and iron(III) ions. Both acids inhibited the Fenton reaction by iron chelation and ROS scavenging in the deoxyribose degradation assay. In the iron(II) autoxidation assay, anthranilic acid showed antioxidant effects, whereas 3-hydroxyanthranilic acid exhibited apparent pro-oxidant activity. The differential pulse voltammograms of free metabolites and their iron(II) coordination complexes reflected these properties. Nano-ESI-MS confirmed ANA and 3-HANA as efficient iron(II) chelators, both of which form coordination complexes of ligand:iron(II) ratio 1:1, 2:1, and 3:1. In addition, nano-ESI-MS analyses of the oxidation effects by hydroxyl radical attack identified 3-HANA as strikingly more susceptible than ANA. 3-HANA susceptibility to oxidation may explain its decreased concentrations in the reaction mixture. The presented observations can add to explaining why 3-HANA levels decrease in patients with some neurological and other diseases which can often associated with elevated concentrations of ROS.
authors.affiliation: Division of Molecular Systems Biology, Department of Ecogenomics and Systems Biology, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, Vienna A-1090, Austria.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Chobot
authors.affiliation: Plant Biochemistry, Albrecht-von-Haller Institut, Georg-August-Universität Göttingen, Justus-von-Liebig-Weg 11, Göttingen D-37077, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Hadacek
authors.affiliation: Division of Molecular Systems Biology, Department of Ecogenomics and Systems Biology, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, Vienna A-1090, Austria.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Weckwerth
authors.affiliation: Division of Molecular Systems Biology, Department of Ecogenomics and Systems Biology, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, Vienna A-1090, Austria.
authors.forename: Lenka
authors.initials: L
authors.lastname: Kubicova
keywords: 3-Hydroxyanthranilic acid:anthranilic acid ratio; Differential pulse voltammetry; Iron coordination complexes; Kynurenines; Mass spectrometry; Reactive oxygen species