Cadmium binding to human α₂-macroglobulin

α₂-Macroglobulin (α₂M) is one of the major cadmium-binding proteins of human plasma. As determined with equilibrium dialysis, α₂M bound 4.6 (±0.7) mol Cd²⁺ per mol protein with an apparent dissociation constant of (9.6 (±5.0))·10^-7M. Methylamine-modified α₂M (α₂M-Me) had a similar affinity for Cd²⁺ (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 α₂M and soybean trypsin inhibitor. Using the binding parameters determined from the equilibrium dialysis studies, the Cd²⁺ concentration which produced a half-maximal increase in amidolytic activity corresponded to saturation of all Cd²⁺-binding sites in one-half of the α₂M molecules. From these results, a model is proposed in which one Cd²⁺-binding site is present in each of the four polypeptide chains which compose α₂M.