title: O2-mediated oxidation of ferrous nitrosylated human serum heme-albumin is limited by nitrogen monoxide dissociation.
abstract: Human serum heme-albumin (HSA-heme-Fe) displays globin-like properties. Here, kinetics of O(2)-mediated oxidation of ferrous nitrosylated HSA-heme-Fe (HSA-heme-Fe(II)-NO) is reported. Values of the first-order rate constants for O(2)-mediated oxidation of HSA-heme-Fe(II)-NO (i.e., for ferric HSA-heme-Fe formation) and for NO dissociation from HSA-heme-Fe(II)-NO (i.e., for NO replacement by CO) are k=9.8 × 10(-5) and 8.3 × 10(-4) s(-1), and h=1.3 × 10(-4) and 8.5 × 10(-4) s(-1), in the absence and presence of rifampicin, respectively, at pH=7.0 and T=20.0 °C. The coincidence of values of k and h indicates that NO dissociation represents the rate limiting step of O(2)-mediated oxidation of HSA-heme-Fe(II)-NO. Mixing HSA-heme-Fe(II)-NO with O(2) does not lead to the formation of the transient adduct(s), but leads to the final ferric HSA-heme-Fe derivative. These results reflect the fast O(2)-mediated oxidation of ferrous HSA-heme-Fe and highlight the role of drugs in modulating allosterically the heme-Fe-atom reactivity.
authors.affiliation: Interdepartmental Laboratory of Electron Microscopy, University Roma Tre, Via della Vasca Navale 79, I-00146 Roma, Italy. ascenzi@uniroma3.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Gullotta
authors.forename: Magda
authors.initials: M
authors.lastname: Gioia
authors.forename: Massimo
authors.initials: M
authors.lastname: Coletta
authors.forename: Mauro
authors.initials: M
authors.lastname: Fasano
mesh_terms: D006418:Heme / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D012709:Serum Albumin; D009569:Nitric Oxide; D006418:Heme; D007501:Iron; D010100:Oxygen