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Enhancing hypothiocyanite production by lactoperoxidase – mechanism and chemical properties of promotors

Background: The heme enzyme lactoperoxidase is found in body secretions where it significantly contributes to the humoral immune response against pathogens. After activation the peroxidase oxidizes
thiocyanate to hypothiocyanite which is known for its microbicidal properties. Yet several pathologies are accompanied by a disturbed hypothiocyanite production which results in a reduced immune defense.
Methods: The results were obtained by measuring enzyme-kinetic parameters using UV–vis spectroscopy and a standardized enzyme-kinetic test system as well as by the determination of second order
rate constants using stopped-flow spectroscopy. Results: In this study we systematically tested thirty aromatic substrates for their efficiency to promote the lactoperoxidase-mediated hypothiocyanite production by restoring the native ferric enzyme state. Thereby hydrophobic compounds with a 3,4-dihydroxyphenyl partial structure such ashydroxytyrosol and selected flavonoids emerged as highly efficient promotors of the (pseudo-)halogenating lactoperoxidase activity. Conclusions: This study discusses important structure-function relationships of efficient aromatic LPO substrates and may contribute to the development of new agents to promote lactoperoxidase activity in
secretory fluids of patients. Significance: This study may contribute to a better understanding of the (patho-)physiological importance of the (pseudo-)halogenating lactoperoxidase activity. The presented results may in future lead to the development of new therapeutic strategies which, by reactivating lactoperoxidase-derived hypothiocyanite production, promote the immunological activity of this enzyme.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa.de:bsz:15-qucosa-206322
Date30 June 2016
CreatorsGau, Jana, Furtmüller, Paul-Georg, Obinger, Christian, Arnhold, Jürgen, Flemmig, Jörg
ContributorsUniversität Leipzig, Medizinische Fakultät, Universität für Bodenkultur Wien, Department für Chemie, Universität Leipzig, Translationszentrum für Regenerative Medizin, Elsevier,
PublisherUniversitätsbibliothek Leipzig
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typedoc-type:article
Formatapplication/pdf
SourceBiochemistry and biophysics reports 4 (2015) 257-267 doi: 10.1016/j.bbrep.2015.10.001

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