The kinetics of the catalytic cycle of myeloperoxidase and of horseradish peroxidase reacting with aminoglycosides have been studied by conventional and stopped-flow spectrophotometry. Aminoglycosides acted as one-electron reducing substrates converting compound I, formed when stoichiometric amounts of hydrogen peroxide were added to the enzyme, to compound II, and compound II to the resting, ferric enzyme. The latter gradually decayed into a further spectroscopic derivative (lambda(max) = 540 and 403 nm) tentatively identified as a complex of ferric heme with the antibiotic oxidation product(s), and the resulting enzyme was fully inactivated. Since myeloperoxidase is the only human enzyme known to convert chloride ions into the cytotoxic hypochlorous acid, the data presented in this paper bear relevance to the pharmacological effects of aminoglycoside antibiotics, which, while inhibiting bacterial growth, also prevent oxidative cellular damage caused by hypochlorous acid aging as substrates and inhibitors of myeloperoxidase.

Aminoglycosides as substrates and inhibitors of peroxidases: a possible role of these antibiotics against myeloperoxidase-dependent cytotoxicity / Lorrai, A.; Padiglia, A.; Medda, R.; Bellelli, Andrea; Arcovito, Alessandro; Floris, G.. - In: JOURNAL OF PROTEIN CHEMISTRY. - ISSN 0277-8033. - STAMPA. - 21:(2002), pp. 97-104. [10.1023/A:1014524227764]

Aminoglycosides as substrates and inhibitors of peroxidases: a possible role of these antibiotics against myeloperoxidase-dependent cytotoxicity

BELLELLI, Andrea;ARCOVITO, Alessandro;
2002

Abstract

The kinetics of the catalytic cycle of myeloperoxidase and of horseradish peroxidase reacting with aminoglycosides have been studied by conventional and stopped-flow spectrophotometry. Aminoglycosides acted as one-electron reducing substrates converting compound I, formed when stoichiometric amounts of hydrogen peroxide were added to the enzyme, to compound II, and compound II to the resting, ferric enzyme. The latter gradually decayed into a further spectroscopic derivative (lambda(max) = 540 and 403 nm) tentatively identified as a complex of ferric heme with the antibiotic oxidation product(s), and the resulting enzyme was fully inactivated. Since myeloperoxidase is the only human enzyme known to convert chloride ions into the cytotoxic hypochlorous acid, the data presented in this paper bear relevance to the pharmacological effects of aminoglycoside antibiotics, which, while inhibiting bacterial growth, also prevent oxidative cellular damage caused by hypochlorous acid aging as substrates and inhibitors of myeloperoxidase.
peroxidase; aminoglicoside antibiotics; antibiotic metabolism
01 Pubblicazione su rivista::01a Articolo in rivista
Aminoglycosides as substrates and inhibitors of peroxidases: a possible role of these antibiotics against myeloperoxidase-dependent cytotoxicity / Lorrai, A.; Padiglia, A.; Medda, R.; Bellelli, Andrea; Arcovito, Alessandro; Floris, G.. - In: JOURNAL OF PROTEIN CHEMISTRY. - ISSN 0277-8033. - STAMPA. - 21:(2002), pp. 97-104. [10.1023/A:1014524227764]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/109159
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