title: Stopped-flow studies on drug-protein binding. 1. Kinetics of warfarin binding to human serum albumin.
abstract: We have studied the binding of warfarin to human serum albumin (HSA) with the stopped-flow method. At 37 degrees C the rate constant for the velocity of dissociation of the stable warfarin-HSA complex is 10 S-1 (t50% = 0.07 s). Concentration and temperature dependent association constants for warfarin binding to HSA have been measured (2.5 x 10(5) M-1 S-1 at 6 degrees C, 9.8 x 10(5) M-1 S-1 at 22 degrees C and 15.3 x 10(5) M-1 S-1 at 37 degrees C). Our experimentally obtained relaxation constants are best explained by the existence of 5 equivalent low affinity binding sites for warfarin on the HSA molecule, each capable of conversion into a high affinity site. The measured energy of activation for this conversion is 57.5 kJ M-1.
mesh_terms: D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013816:Thermodynamics; D014859:Warfarin / Q000097:blood*
chemical_list: D012709:Serum Albumin; D014859:Warfarin