The effect of albumin conformation on the binding of warfarin to human serum albumin. The dependence of the binding of warfarin to human serum albumin on the hydrogen, calcium, and chloride ion concentrations as studied by circular dichroism, fluorescence, and equilibrium dialysis.
The pH dependence of the binding of warfarin to human serum albumin has been studies by circular dichroism, fluorescence, and equilibrium dialysis. The pH dependences of the induced ellipticity and the fluorescent intensity of the warfarin . albumin complexes at low drug to protein ratios parallel the neutral to base transition, occurring in the protein over the pH range 6 to 9. Dialysis data show albumin to have a single high affinity site for warfarin over this pH range. This affinity is higher for the basic than for the neutral conformation. Calcium ions increase the high affinity constant of warfarin for albumin over the same pH region, by affecting the neutral to base transition. On the other hand, chloride ions reduce the induced ellipticity and the fluorescent intensity of the complexes at all pH investigated, the mechanism being primarily that of displacement of the drug from albumin.
D001665:Binding Sites; D002118:Calcium; D002712:Chlorides; D002942:Circular Dichroism; D003956:Dialysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008433:Mathematics; D011485:Protein Binding; D011487:Protein Conformation; D012709:Serum Albumin; D013050:Spectrometry, Fluorescence; D014859:Warfarin
D002712:Chlorides; D012709:Serum Albumin; D014859:Warfarin; D002118:Calcium