Peroxynitrite detoxification by ferryl Mycobacterium leprae truncated hemoglobin O

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-Fe(IV)=O), obtained by treatment with H2O2, is reported. Values of the second-order rate constant for peroxynitrite detoxification by Ml-trHbO-Fe(IV)=O (i.e., of Ml-trHbO-Fe(III) formation; k(on)), at pH 7.2 and 22.0 degrees C, are 1.5 x 10(4) M (1) s(-1), and 2.2, 10(4) M-1 s(-1), in the absence of and presence of physiological levels of CO2 (similar to 1.2 x 10(-3) M), respectively. Values of k(on) increase on decreasing pH with a pK(a) value of 6.7. this suggests that ONOOH reacts preferentially with Ml-trHbO-Fe(IV)=O. In turn, peroxynitrite acts as an antioxidant of Ml-trHbO-Fe(IV)=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. (C) 2009 Elsevier Inc. All rights reserved.