Characterization of zinc-binding proteins of plasma in familial hyperzincemia

Plasmas from three brothers (aged 35 to 45) with chronic hyperzincemia (325 to 525 micrograms/dl Zn) were analyzed and compared with pooled control plasma (104 microgram/dl Zn). The levels of copper, iron, total protein, albumin, and amino acids were similar in normal and hyperzincemic plasmas. Distribution of zinc among plasma components was determined chromatographically. Zinc eluted quantitatively in two distinct peaks from Sephadex G-100 gel filtration resin. The amount of the metal in fractions containing species larger than 100,000 molecular weight (peak I) was similar (35 to 45 micrograms/dl Zn) in normal and hyperzincemic plasmas. The additional complement of zinc in hyperzincemic plasma was localized within fractions containing zinc-binding proteins such as albumin, transferrin and HRG. That zinc was not associated with transferrin was determined by Affi-Gel affinity chromatography. The amounts of HRG in hyperzincemic plasmas were similar to or below those in control plasma. Zinc and albumin were selectively retained by anti-human albumin IgG coupled to protein A-Sepharose. In contrast, anti-human HRG IgG coupled to CM Bio-Gel A failed to bind plasma zinc. The findings indicate that (1) most available, protein-associated zinc in normal plasma is bound to albumin and (2) the additional complement of zinc in familial hyperzincemic plasma is associated with albumin. The biochemical basis for the enhanced binding of zinc by albumin in hyperzincemic plasma is unknown.