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 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) × 103 M−1 s−1 in the absence of CO2 and abacavir, (1.3 ± 0.2) × 105 M−1 s−1 in the presence of CO2, (2.2 ± 0.2) × 104 M−1 s−1 in the presence of abacavir, and (3.6 ± 0.3) × 105 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) × 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).