title: Abacavir modulates peroxynitrite-mediated oxidation of ferrous nitrosylated human serum heme-albumin.
abstract: Human serum albumin (SA) is best known for its extraordinary ligand-binding capacity. Here, kinetics of peroxynitrite-mediated oxidation of SA-heme(II)-NO is reported. Peroxynitrite reacts with SA-heme(II)-NO leading to SA-heme(III) and ()NO by way of the transient SA-heme(III)-NO species. Abacavir facilitates peroxynitrite-mediated oxidation of SA-heme(II)-NO, in the absence and presence of CO2. Values of the second order rate constant for peroxynitrite-mediated oxidation of SA-heme(II)-NO are (6.5+/-0.9) x 10(3) M(-1) s(-1) in the absence of CO2 and abacavir, (1.3+/-0.2) x 10(5) M(-1) s(-1) in the presence of CO2, (2.2+/-0.2) x 10(4) M(-1) s(-1) in the presence of abacavir, and (3.6+/-0.3) x 10(5) M(-1) s(-1) in the presence of both CO2 and abacavir. The value of the first-order rate constant for *NO dissociation from the SA-heme(III)-NO complex (=(1.8+/-0.3) x 10(-1) s(-1)) is CO2- and abacavir-independent, representing the rate-limiting step. Present data represent the first evidence for the allosteric modulation of SA-heme reactivity by heterotropic interaction(s).
authors.affiliation: Department of Biology, 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: Mauro
authors.initials: M
authors.lastname: Fasano
mesh_terms: D015224:Dideoxynucleosides / Q000737:chemistry*; D006418:Heme / Q000737:chemistry*; D006801:Humans; D007501:Iron / Q000737:chemistry*; D007536:Isomerism; D007700:Kinetics; D009569:Nitric Oxide / Q000737:chemistry*; D009603:Nitroso Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*; D000099227:Abacavir
chemical_list: D015224:Dideoxynucleosides; D006418:Heme; D007501:Iron; D009569:Nitric Oxide; D009603:Nitroso Compounds; D030421:Peroxynitrous Acid; D012709:Serum Albumin; D000099227:Abacavir