The accretion of copper and of zinc by the foetuses of prolific ewes.
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Biomedical subjects
Publications and source records attributed to I Bremner.
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The effects of dietary cadmium on copper and zinc metabolism in animals are described. Emphasis is given to situations involving chronic exposure to low levels of cadmium, to the identification of population groups most at risk, and to the protective effect of dietary supplementation with copper and zinc. The mechanism of the interaction between the metals and the involvement of metallothionein are discussed.
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A study has been made of the distribution of copper in the kidneys of copper-poisoned sheep, containing up to 240 microgram copper/g fresh cortex. About 64% of the copper in the cortex was present in the cytosol and 75% of this occurred in a form with molecular weight of approx. 12 000. This was partially purified by gel filtration on Sephadex G-75 and Bio-Gel P.10 and ion exchange chromatography on DEAE Sephadex A-25 to give three sub-fractions, which also contained zinc. The amino acid composition, copper content and chromatographic behaviour of these proteins indicated that they were copper-thioneins. No significant amounts of the proteins were detected in the plasma or erythrocytes of the copper-poisoned sheep when they were undergoing the haemolytic crisis typical of this syndrome. It is concluded that metallothionein constitutes the major copper-binding protein in the kidneys of copper-poisoned sheep. However the rapid accumulation of the protein in the kidney, and the development of kidney damage, are unlikely to have arisen from the release of the intact copper-protein from the liver and its transport via the blood to the kidneys.
1. A study has been made of the copper- and zinc-binding proteins in the livers from sheep foetuses of 80-142 d gestational age. 2. Metallothionein was found to constitute the major Zn-binding component in the cytosol at all times and to be identical to Zn-thionein from adult sheep liver. 3. Zn also occurred in two fractions, not normally found in sheep liver, with approximate molecular weights of 28000 and 47000. The relative proportions of these were age-dependent. 4. Between 15 and 35% of the hepatic Cu, corresponding to most of the Cu in the cytosol, also occurred in the metallothionein-containing fraction.
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Calves have been raised for veal on liquid diets containing different amounts of iron. A concentration of 25-30 mg soluble iron/kg dietary dry matter provided sufficient haemaglobin for normal appetite, growth and oxygen transport, and also produced carcases light coloured enough for the veal trade. When anaemia was induced in calves or sheep the first measurable response from the animals was a fall in appetite which provided a more sensitive indicator than more complicated physiological or biochemical measurements.
The mixed copper- and zinc-binding proteins, with mol.wt. of approx. 12000, induced in rat liver after injection of copper were isolated and characterized as metallothioneins. Three separate forms were obtained, with 7-11% total metal in the protein, equivalent to 2.6-1.6 cysteine residues/metal atom.
The copper-binding proteins with mol. wt. of approx. 12000 in the cytosol of pig liver have been identified as copper-thioneins. They contain variable amounts of zinc, with approx. 10% total metal in the protein. The molar cysteine/metal ratio is approx. 2:1.
1. A study has been made by gel filtration techniques of the soluble copper- and zinc-binding proteins in livers from pigs of different Zn status. 2. The distribution of both Cu and Zn between the three fractions isolated was greatly influenced by the Zn status of the animal. In livers from pigs given a Zn-supplemented diet the proportion of either Cu or Zn found in the fraction with a molecular weight of about 12 000 (fraction 3) was a direct function of the total liver concentration of the metal. In livers from pigs given a low-Zn diet, only small amounts of Cu or Zn were present in this fraction, regardless of liver Cu content. 3. These results suggest that Zn may be essential for the stabilization of the metal-binding protein in this fraction.
1. A study has been made by gel-filtration techniques of the soluble copper- and zinc-binding proteins in rat liver after both intraperitoneal injection of Cu and dietary Cu supplementation. 2. Liver Cu and Zn concentrations increased after injection of Cu, both metals accumulating in the cytosol, mainly in a fraction with an apparent molecular weight of about 12 000. 3. When Zn-deficient rats were injected with Cu, there was little change in liver Zn concentration and the occurence of Cu in the low-molecular-weight form (about 12 000) was more transient. At most periods after injection, Cu accumulated mainly in a fraction with a molecular weight greater than 65 000. 4. When the rats were Cu-loaded by dietary supplementation, virtually no Cu or Zn was found in the low-molecular-weight form in Zn-deficient rats, although they were found in the Zn-supplemented animals. 5. The results suggest that Zn is essential for the accumulation of Cu in this form, but not for Cu to stimulate production of the metal-binding protein by a process requiring active protein protein synthesis.
1. A study has been made of the effects of dietary zinc supplementation on the development of copper toxicosis in three groups each of eight 12-week-old lambs. 2. None of the lambs receiving 420 mg Zn/kg diet developed Cu toxicosis in the 24-week experimental period, compared with three in the control group receiving 43 mg Zn/kg and possibly one in the group receiving 220 mg Zn/kg. 3. Liver Cu concentrations were reduced by up to 40% in the Zn-supplemented animals, with concomitant reductions, especially in the early stages of the experiment, in the extent of liver damage, as assessed by measurement of plasma aspartate aminotransferase (EC 2.6.1.1) and arginase (EC 3.5.3.1) activities. 4. Plasma and liver Zn concentrations were increased only slightly in the lambs receiving the Zn-supplemented diets, and the only indication of possible toxic effects of the Zn supplements was the development of a slight anaemia in those animals receiving 420 mg Zn/kg diet. 5. The results suggest that the incidence of Cu toxicosis in sheep may be controlled by increasing their dietary Zn intake.
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The isolation of two forms of hepatic zinc-thioneins after either zinc injection into rats or partial restriction of their food intake is described. The proteins differed slightly in their amino acid composition and electrophoretic mobilities. Increases in liver zinc content after both treatments were synchronous with, and associated almost completely with, increased zinc-binding to these proteins. The time-course for the appearance and disappearance of the zinc proteins is shown. It is suggested that metallothionein is involved in the normal metabolism of zinc, perhaps in some temporary storage or detoxication capacity.
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