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. © 2009 Elsevier Inc. All rights reserved.
Peroxynitrite detoxification by ferryl Mycobacterium leprae truncated hemoglobin O / Ascenzi, P.; De Marinis, E.; Visca, P.; Ciaccio, C.; Coletta, M.. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - 380:2(2009), pp. 392-396. [10.1016/j.bbrc.2009.01.088]
Peroxynitrite detoxification by ferryl Mycobacterium leprae truncated hemoglobin O
De Marinis E.;
2009
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. © 2009 Elsevier Inc. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
