AJP - Endocrinology and Metabolism, Vol 261, Issue 1 E115-E125, Copyright © 1991 by American Physiological Society
Kinetics of copper metabolism in rats: a compartmental model
M. A. Dunn, M. H. Green and R. M. Leach Jr
Department of Poultry Science, Pennsylvania State University, University Park 16802.
Model-based compartmental analysis was used to describe data on the whole
body kinetics of copper metabolism in rats. Data were collected on recovery
of radio-copper in plasma, liver, skin, skeletal muscle, bile, and feces
for 3 days after the injection of 10 micrograms iv of copper labeled with
64Cu. Data on copper masses and on 64Cu kinetics were analyzed by the
stimulation, analysis, and modeling computer programs. Observed data were
fit to a 16-component "working hypothesis" model; fractional transfer
coefficients were estimated, and steady-state compartment masses and copper
transfer rates were calculated. The model postulates a rapid turnover of
plasma nonceruloplasmin (NCp) copper (8.5 h-1), which exchanged a large
amount of copper with extrahepatic tissues (16 micrograms/h) as well as
liver (13 micrograms/h). In comparison, ceruloplasmin (Cp) transferred
relatively little copper to tissues (less than 1 microgram/h). NCp copper
is postulated to be the precursor for biliary copper. Regarding the
intracellular metabolism of copper in hepatic and extrahepatic tissues, the
data were compatible with a faster turning-over compartment that exchanged
copper with NCp and a slower turning-over compartment with input from Cp.
In the liver, the slower turning-over compartment was the copper present in
peak II (mol mass 30,000-40,000 Da); this received much of its input from
the faster turning-over compartment (peak III), which was hypothesized to
represent, in large part, copper in metallothionein.
