Modulation of activity of lactoperoxidase and myeloperoxidase

Modulation of Activity of Lactoperoxidase and Myeloperoxidase

Due to local conditions (e.g. excess H2O2, lack of SCN-) in the buccal cavity the (pseudo-)halogenating enzymatic activity of the heme peroxidase lactoperoxidase (LPO) may be inactivated. Thereby the accumulation of those enzymatic redox intermediates is assumed which are not able to two-electronically oxidize thiocyanate (SCN-) to hypothiocyanite (-OSCN). An impaired production of this antimicrobial enzymatic product leads to e.g. oral infections.

In many subsequent studies we explored the physicochemical properties of those organic LPO substrates which, by regenerating the native enzymatic state, promote the -OSCN formation by the enzyme. Thereby especially hydrophobic substrates (e.g. flavonoids) with a 3,4-dihydroxyphenyl partial structure were shown to efficiently promote the pseudo-halogenating lactoperoxidase activity. The results were confirmed by stopped flow-kinetic measurements.

While under physiological conditions lactoperoxidase almost exclusively oxidizes SCN- the leukocyte-derived enzyme myeloperoxidase (MPO) also two-electronically oxidizes chloride (Cl-) to hypochlorous acid (HOCl). This enzymatic product contributes to the humoral immune defence of especially neutrophil granulocytes in the blood but also leads to e.g. tissue destruction during long-lasting and/or excess inflammatory reactions. Therefore we currently also test MPO activity inhibitors both in vitro as well as in neutrophil granulocytes. These studies are conducted in cooperation with colleagues from Brussels and Vienna and may lead to the development of new drugs for the treatment of chronic inflammatory diseases.

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Team Members

Dr. Jörg Flemmig, Jana Gau, Prof. Dr. Jürgen Arnhold

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Collaborations

Prof. Dr. Christian Obinger
University of Natural Resources and Life Sciences
Vienna, Austria

 

Prof. Dr. Pierre van Antwerpen
Universite Libre de Bruxelles
Brussels, Belgium

letzte Änderung: 10.07.2017