Peroxynitrite detoxification by ferryl Mycobacterium leprae truncated hemoglobin O

Paolo Ascenzi, Elisabetta De Marinis, Paolo Visca, Chiara Ciaccio, Massimo Coletta

Research output: Contribution to journalArticle

Abstract

During infection, Mycobacterium leprae is faced with the host macrophagic environment limiting the growth of the bacilli. However, (pseudo-)enzymatic detoxification systems, including truncated hemoglobin O (Ml-trHbO), could allow this mycobacterium to persist in vivo. Here, kinetics of peroxynitrite (ONOOH/ONOO-) detoxification by ferryl Ml-trHbO (Ml-trHbO{single bond}Fe(IV){double bond, long}O), obtained by treatment with H2O2, is reported. Values of the second-order rate constant for peroxynitrite detoxification by Ml-trHbO{single bond}Fe(IV){double bond, long}O (i.e., of Ml-trHbO{single bond}Fe(III) formation; kon), at pH 7.2 and 22.0 °C, are 1.5 × 104 M-1 s-1, and 2.2 × 104 M-1 s-1, in the absence of and presence of physiological levels of CO2 (∼1.2 × 10-3 M), respectively. Values of kon increase on decreasing pH with a pKa value of 6.7, this suggests that ONOOH reacts preferentially with Ml-trHbO{single bond}Fe(IV){double bond, long}O. In turn, peroxynitrite acts as an antioxidant of Ml-trHbO{single bond}Fe(IV){double bond, long}O, which could be responsible for the oxidative damage of the mycobacterium. As a whole, Ml-trHbO can undertake within the same cycle H2O2 and peroxynitrite detoxification.

Original languageEnglish
Pages (from-to)392-396
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume380
Issue number2
DOIs
Publication statusPublished - Mar 6 2009

Keywords

  • Carbon dioxide
  • Detoxification of reactive nitrogen and oxygen species
  • Hydrogen peroxide
  • Mycobacterium leprae
  • Peroxynitrite
  • Truncated hemoglobin O

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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