Cadmium binding to human α 2-macroglobulin

Abstract

α 2-Macroglobulin (α 2M) is one of the major cadmium-binding proteins of human plasma. As determined with equilibrium dialysis, α 2M bound 4.6 (±0.7) mol Cd 2+ per mol protein with an apparent dissociation constant of (9.6 (±5.0))·10 −7M. Methylamine-modified α 2M (α 2M-Me) had a similar affinity for Cd 2+ ( K d, app = 5.3·10 −7M, but fewer binding sites. Cadmium produced a small increase in the amidolytic activity of trypsin in the presence of α 2M and soybean trypsin inhibitor. Using the binding parameters determined from the equilibrium dialysis studies, the Cd 2+ concentration which produced a half-maximal increase in amidolytic activity corresponded to saturation of all Cd 2+-binding sites in one-half of the α 2M molecules. From these results, a model is proposed in which one Cd 2+-binding site is present in each of the four polypeptide chains which compose α 2M.