01898nas a2200301   4500000000100000008004100001260001600042653001200058653002300070653001600093653001100109653002200120653002800142653001200170653002500182653002300207653002600230100001400256700001700270700001200287700001400299700001400313245008800327300001000415490000800425520114900433022001401582       2009                            d  c2009 Mar 0610aAnimals10aBacterial Proteins10aHemoglobins10aHumans10aHydrogen Peroxide10aInactivation, Metabolic10aleprosy10aMycobacterium leprae10aPeroxynitrous Acid10aTruncated Hemoglobins1 aAscenzi P1 aDe Marinis E1 aVisca P1 aCiaccio C1 aColetta M00aPeroxynitrite detoxification by ferryl Mycobacterium leprae truncated hemoglobin O.  a392-60 v3803 a<p>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 H(2)O(2), 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 1.5x10(4) M(-1) s(-1), and 2.2x10(4) M(-1) s(-1), in the absence of and presence of physiological levels of CO(2) (approximately 1.2x10(-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 H(2)O(2) and peroxynitrite detoxification.</p>  a1090-2104