Ibuprofen and warfarin modulate allosterically ferrous human serum heme-albumin nitrosylation

Paolo Ascenzi, Yu Cao, Grazia R. Tundo, Massimo Coletta, Gabriella Fanali, Mauro Fasano

Research output: Contribution to journalArticle

Abstract

Ferrous human serum heme-albumin (HSA-heme-Fe(II)) displays globin-like properties. Here, the effect of ibuprofen and warfarin on kinetics of HSA-heme-Fe(II) nitrosylation is reported. Values of the second-order rate constant for HSA-heme-Fe(II) nitrosylation (kon) decrease from 6.3×106M-1s-1 in the absence of drugs, to 4.1×105M-1s-1 and 4.8×105M-1s-1, in the presence of saturating amounts of ibuprofen and warfarin, respectively, at pH 7.0 and 20.0°C. From the dependence of kon on the drug concentration, values of the dissociation equilibrium constant for ibuprofen and warfarin binding to HSA-heme-Fe(II) (i.e., K=3.2×10-3M and 2.6×10-4M, respectively) were determined. The observed allosteric effects could indeed reflect ibuprofen and warfarin binding to the regulatory fatty acid binding site FA2, which brings about an alteration of heme coordination, slowing down HSA-heme-Fe(II) nitrosylation. Present data highlight the allosteric modulation of HSA-heme-Fe(II) reactivity by heterotropic effectors.

Original languageEnglish
Pages (from-to)185-189
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume411
Issue number1
DOIs
Publication statusPublished - Jul 22 2011

Keywords

  • Allostery
  • Ferrous human serum heme-albumin
  • Ibuprofen-dependent HSA-heme-Fe(II) nitrosylation
  • Kinetics
  • Thermodynamics
  • Warfarin-dependent HSA-heme-Fe(II) nitrosylation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Ibuprofen and warfarin modulate allosterically ferrous human serum heme-albumin nitrosylation'. Together they form a unique fingerprint.

  • Cite this