Abacavir modulates peroxynitrite-mediated oxidation of ferrous nitrosylated human serum heme-albumin

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)-N-. 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 9f 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)-N-. 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). (c) 2006 Elsevier Inc. All rights reserved.