Graduate Thesis Or Dissertation
 

Metabolism of copper in blood and liver as influenced by species and diet

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  • Copper in blood and liver can be divided into several fractions. Copper in blood is about evenly divided between erythrocytes and plasma. Normal concentrations for most species range between one and two parts per million. Plasma copper is mainly a copper protein, ceruloplasmin and a loosely bound form, reacting directly with Na diethyldithiocarbamate (DR Cu). In livers of normal rats (ca. 18 ppm Cu) the distribution is: debris, 12.8%; mitochondria, 13.5%; microsomes, 17.9%; and soluble fraction, 54.8%. On the other hand, in cattle with higher liver copper levels (ca. 69.5 ppm) the distribution is: debris, 22.2%; mitochondria, 12.3%; microsomes, 14.6%; and soluble fraction, 50.9%. The distributions are influenced by dietary copper in rats fed rations containing from 1 ppm to 200 ppm Cu. Erythrocyte and DR Cu appeared to be directly related to the copper intake, with values ranging from 0.95 to 2.04 μg/ml and 0.19 to 1.52 μg respectively. Ceruloplasmin values were depressed in the low ration (6.6 IU) and remained constant with Cu intakes greater than 10 ppm (35 IU). Liver Cu levels were depressed in the low (1 ppm intake) group (10 ppm), "normal" in the range of 10-100 ppm intake (20 ppm) and elevated with 200 ppm intake (69 ppm). The distribution in the liver fractions was affected by copper content, with the soluble fraction being the most sensitive to changes in liver copper. The debris increased relatively little in copper content. The copper status of the rat greatly influenced the metabolism of injected ⁶⁴Cu. In all cases, radiocopper was removed rapidly from the plasma and concentrated in the liver. The incorporation of copper-64 in the liver was directly related to the copper status of the rat (low, "normal", high). There was a subsequent increase in blood activities and a reduction of liver copper after four hours in the low and "normal" groups. The increase in the blood radioactivity corresponded to an increase in ceruloplasmin activity in rats maintained on a low copper ration. The relative distribution of radioactivity in the liver fractions of "normal" rats at all time intervals was as follows: soluble > debris > mitochondria > microsomes. There were significant deviations in rats on low or high copper rations. Pathways for the movement of copper in the blood and liver in the various species are discussed.
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