1. Warfarin inhibits allosterically the reductive nitrosylation of ferric human serum heme-albumin.
- Author
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Ascenzi P, Bocedi A, Gioia M, Fanali G, Fasano M, and Coletta M
- Subjects
- Heme chemistry, Humans, Hydrogen-Ion Concentration, Iron chemistry, Kinetics, Ligands, Nitric Oxide chemistry, Oxidation-Reduction, Protein Binding, Serum Albumin, Human chemistry, Thermodynamics, Warfarin, Heme metabolism, Nitric Oxide metabolism, Serum Albumin, Human metabolism
- Abstract
Human serum heme-albumin (HSA-heme-Fe) displays heme-based ligand binding and (pseudo-)enzymatic properties. Here, the effect of the prototypical drug warfarin on kinetics and thermodynamics of NO binding to ferric and ferrous HSA-heme-Fe (HSA-heme-Fe(III) and HSA-heme-Fe(II), respectively) and on the NO-mediated reductive nitrosylation of the heme-Fe atom is reported; data were obtained between pH5.5 and 9.5 at 20.0°C. Since warfarin is a common drug, its effect on the reactivity of HSA-heme-Fe represents a relevant issue in the pharmacological therapy management. The inhibition of NO binding to HSA-heme-Fe(III) and HSA-heme-Fe(II) as well as of the NO-mediated reductive nitrosylation of the heme-Fe(III) atom by warfarin has been ascribed to drug binding to the fatty acid binding site 2 (FA2), shifting allosterically the penta-to-six coordination equilibrium of the heme-Fe atom toward the low reactive species showing the six-coordinated metal center by His146 and Tyr161 residues. These data: (i) support the role of HSA-heme-Fe in trapping NO, (ii) highlight the modulation of the heme-Fe-based reactivity by drugs, and (iii) could be relevant for the modulation of HSA functions by drugs in vivo., (Copyright © 2017 Elsevier Inc. All rights reserved.) more...
- Published
- 2017
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