organ Zn were simulated for growing rats receiving adequate (Fig. 8.12) or deficient (Fig. 8.13) dietary Zn. Rats fed a deficient Zn diet accumulated less Zn overall in tissues, but muscle accumulated relatively more zinc than the other tissues, mainly at the expense of bone. The tissue distribu- tion of Zn shown at day 28 in Figs 8.12 and 8.13 is from Giugliano and Millward (1984). The redistribution of Zn was simulated using modelling techniques for regulating Zn tissue mass as described above. The rate of redistribution was assumed to take about one-half of the 28- day period simulated, which is consistent with the time course of 65Zn redistribution observed in another study with marginally deficient rats.
and other gastrointestinal secretions, with only a small percentage of endogenous loss in the urine. Surface losses from sweat, skin and hair or feathers are small, but exceed urinary losses, at least in humans.
Biliary Cu is reabsorbed poorly in mammals and chickens, which increases the efficiency of endogenous excretion.
The liver plays an important role in the quantitative whole-body metabolism of Cu, especially in ruminants. Up to 80% of whole-body Cu is found in the liver of healthy sheep and cattle, as opposed to 8 or 9% in the liver of monogastrics. Bone also is a major Cu pool in all species, varying in Cu content from about 18% of whole-body Cu in cattle to 40% in humans.
Muscle comprises about 13% of whole- body Cu in cattle, 23% in humans and 31% in rats. In small animals, the skin also becomes a major component of whole-body Cu, about 23% in rats.
There is considerable variability among species in their ability to maintain liver Cu homeostasis (Fig. 8.14). Sheep
appear to have little or no ability to regulate liver Cu concentration. Even small increments in dietary Cu to unsupple- mented diets yield substantial increases in liver Cu. Sheep are very susceptible to chronic Cu poisoning, which is probably a result of their inability to regulate liver Cu accumulation. Pre-ruminant calves, which also are susceptible to chronic Cu poison- ing, have a limited ability to control liver Cu accumulation, although that ability improves after weaning. Although the liver Cu of adult cattle increases with increasing Cu supplementation above the nutritional requirement, the concentration tends to level off at subtoxic accumulations, indicating some homeostatic regulation.
Rats, on the other hand, demonstrate the same characteristic plateau in response to increasing dietary intake as has been observed with Zn. Liver Cu increases up to the nutritional requirement of about 5–10 µg Cu g1diet and thereafter remains constant up to about 100 µg Cu g1 diet, beyond which a substantial increase in Fig. 8.13. Tissue Zn accumulation of young growing male rats fed deficient dietary Zn (3 µg g1) in a semi-synthetic diet. The figure is a simulation as described in Fig. 8.12.
liver Cu occurs. Laying hens maintain a constant liver Cu concentration up to a relatively high dietary concentration of 600 µg Cu g1 diet, above which homeo- static control breaks down. Ponies also have an ability to maintain Cu homeostasis over a range of dietary intake.
Absorption of Cu decreases with increasing dietary Cu concentration. The results of a number of studies of dietary Cu absorption by humans were compiled by Turnlund (1989) and show an exponential reduction in absorption from about 55% in humans consuming 0.8 mg Cu day1 to about 15% in humans consuming about 7.5 mg day1. Apparent and true absorp- tion of Cu by rats also decreases with increasing dietary intake (e.g. Johnson and Lee, 1988). While the coefficient of true absorption decreased about twofold in rats fed 21 compared with 0.4 µg Cu g1 diet, endogenous Cu excretion increased from 1 to 46 µg g1 (Johnson and Lee, 1988).
These results and others show that rats are
efficient at conserving Cu when fed a defi- cient diet. The response is similar to that found with Zn and Mn. The biological half- life of 67Cu decreased from 2.36 to 1.96 days with increasing dietary Cu concentra- tion in the study of Johnson and Lee (1988), indicating that turnover of tissue Cu accelerated with increasing absorbed Cu. It appears that only intestinal endoge- nous losses are important in homeostatic regulation of Cu, since urinary and salivary Cu were unaffected by changes in dietary Cu in humans. Biliary Cu secretion increases with increasing dietary Cu in rats, cattle and chickens, but not in sheep.
At adequate Cu intakes, changes in absorp- tion may play less of a role than endoge- nous faecal excretion in maintaining Cu homeostasis. Endogenous excretion of Cu by humans was reduced from 1.0 to 0.5 mg day1 when dietary intake was reduced from 1.4 to 0.9 mg day1, while there was no measurable change in percentage absorption of Cu (Milne et al., 1990).
Fig. 8.14. Affect of dietary Cu concentration on liver Cu accumulation by animals. Data were taken from the published reports indicated. Mean data are plotted as symbols. Data extracted from graphs are plotted without symbols. Dietary Cu for cattle (Stoszek et al., 1986) is supplemental Cu without the basal diet contribution.
Simulations of Cu metabolism in humans also predict quantitatively greater changes in endogenous excretion than absorption in response to changes in dietary intake (Buckley, 1996).