title: Peroxynitrite detoxification by ferryl Mycobacterium leprae truncated hemoglobin O.
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-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.
authors.affiliation: Department of Biology and Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, Viale Guglielmo Marconi 446, I-00146 Roma, Italy. ascenzi@uniroma3.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: De Marinis
authors.forename: Paolo
authors.initials: P
authors.lastname: Visca
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciaccio
authors.forename: Massimo
authors.initials: M
authors.lastname: Coletta
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008658:Inactivation, Metabolic; D007918:Leprosy / Q000378:metabolism / Q000382:microbiology*; D009166:Mycobacterium leprae / Q000187:drug effects / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D054793:Truncated Hemoglobins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D006454:Hemoglobins; D054793:Truncated Hemoglobins; C517773:ferrylhemoglobin; C460871:truncated hemoglobin, Mycobacterium leprae; D030421:Peroxynitrous Acid; D006861:Hydrogen Peroxide