Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 411, Issue 1, Pages 185-189Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2011.06.130
Keywords
Ferrous human serum heme-albumin; Ibuprofen-dependent HSA-heme-Fe(II) nitrosylation; Warfarin-dependent HSA-heme-Fe(II) nitrosylation; Kinetics; Thermodynamics; Allostery
Categories
Funding
- University Roma Tre, Roma, Italy
Ask authors/readers for more resources
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 (k(on)) decrease from 6.3 x 10(6) M(-1) s(-1) in the absence of drugs, to 4.1 x 10(5) M(-1) s(-1) and 4.8 x 10(5) M(-1) s(-1), in the presence of saturating amounts of ibuprofen and warfarin, respectively, at pH 7.0 and 20.0 degrees C. From the dependence of k(on) 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 x 10(-3) M and 2.6 x 10(-4) M, 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. (C) 2011 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available