Metal-protein interactions in transport, accumulation, and excretion of metals.

The binding of Cu(II), Zn(II), Ni(II), and Cd(II) to protein components in serum, placenta, kidney, and urine was investigated at physiological pH, using radioisotopes as tracers. All the four metals were bound to albumin and other macromolecules in serum. However, small amounts were also bound to low molecular weight components of the size 1500-10000 daltons. The nature of the Cu(II)-binding to alpha-fetoprotein suggests its important role as the Cu(II)-transporting protein in fetal life. Metal binding to placental components were studied using both rat placenta and isolated human trophoblast cells. Studies of metal binding targets in kidney resulted in the isolation of a 4000 daltons acidic polypeptide which binds Ni(II) and Cd(II) with Kapp = 1.1 x 10(-5) and 2.3 x 10(-5), respectively. Studies of metal binding substances in urine reveals the major amounts of these metals binding to substances of molecular weight 500-5000 daltons. Preliminary amino acid analysis suggests these components rich in acidic amino acids, similar to what has been found with kidney polypeptide. There may be a general role for such compounds in the handling of metals in the process of excretion.