Copper transport in rats involving a new plasma protein

Abstract

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.

Integrated physiological response of tilapia, Oreochromis mossambicus, to sublethal copper exposure

“…Cu treatment of fish blood in vitro also resulted in association of Cu with plasma rather than with the blood cell fraction (Buckley et al, 1984). In the blood of mammals, Cu immediately binds to albumin and transcuprein, and is transported to the liver, where it is bound to ceruloplasmin, released into the blood, and distributed to other tissues (Weiss and Linder, 1985;Cousins, 1985). Cu bound to ceruloplasmin constitutes the larger part (90-95%) of plasma Cu, which makes ceruloplasmin the principal Cu transport protein in mammals (Frieden, 1979;Nederbragt et al, 1984).…”

Review of Copper Deficiency and Metabolism in Ruminants

“…In the rat, it appears to serve as the only significant source ofCu for tissues other than liver and kidney (Weiss and Linder 1985 (Weiss and Linder 1985). Albumin-and regarded as the most important quantitatively transcuprein-bound Cu is cleared rapidly by (Kressner et al 1984;Gross et al 1989).…”

“…Albumin-and regarded as the most important quantitatively transcuprein-bound Cu is cleared rapidly by (Kressner et al 1984;Gross et al 1989). the liver (Weiss and Linder 1985).…”

Copper and its inorganic compounds [MAK Value Documentation, 2006]

“…The required copper intake for an adult is about 1 to 3 mg/day. Copper reaches the liver mainly bound to transcuprein (Weiss and Linder 1985), histidine and high affinity binding sites of albumin (Masuoka et al 1993). Copper uptake by liver cells is not an entirely clear process, although one specific copper transport protein, hCTR1 (human chymotrypsin-like protease) nevertheless does seem to play an important role (Peña et al 1999).…”