Copper transport in rats involving a new plasma protein.
The time course of distribution of high-specific activity 67CuCl2 to tissues and plasma components was followed in adult, female rats. Immediately after intubation or injection, tracer 67Cu associated with two components of the blood plasma separable on columns of Sephadex G-150: albumin and another (larger) component, which was not ceruloplasmin. The latter, tentatively named transcuprein, had an apparent molecular weight of 270,000 and a high affinity for Cu2+, as judged by processing through Chelex-100, dilution, and exchange with albumin copper, in vitro and in vivo. It was capable of donating copper to tumor cells in serum-free medium. Analysis of "cold" plasma by furnace atomic absorption confirmed the presence of 10-15% of plasma copper in this peak. Plots of percent dose and 67Cu specific activity against time showed that copper followed a very specific pathway after binding to albumin and transcuprein, entering mainly the liver, then reappearing in the plasma on ceruloplasmin, and then achieving peak distribution in peripheral tissues (muscles, brain, etc.). 67Cu disappeared from liver and kidney with an apparent half-life of 4.5 days, the same exponential rate found for whole body turnover. Apparent turnover of ceruloplasmin copper was more rapid. Even after 7-12 days, tracer copper in plasma was still found exclusively with ceruloplasmin. The results indicate that copper follows a carefully prescribed path, on entering the blood and binding to a new transport protein.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood*; D002570:Ceruloplasmin / Q000378:metabolism; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003300:Copper; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D049690:History, Ancient; D005779:Immunodiffusion; D051379:Mice; D008807:Mice, Inbred BALB C; D011868:Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism; D014018:Tissue Distribution
D001798:Blood Proteins; D002352:Carrier Proteins; D011868:Radioisotopes; D012709:Serum Albumin; C023548:copper-binding protein; D003300:Copper; D002570:Ceruloplasmin