C. J. Gubler

STUDIES ON COPPER METABOLISM. IX. THE TRANSPORTATION OF COPPER IN BLOOD

The isolation and identification of the copper protein from serum have clarified the problem of the nature of serum copper (1, 2). This blue protein, ceruloplasmin, is an a-globulin with a molecular weight of approximately 151,000 and contains eight atoms of copper. Ceruloplasmin has true oxidase activity and since it acts on paraphenylene diamine and polyphenols but not on monophenols and monoamines, it has been classified as a laccase (3, 4). Most if not all of the copper in normal human or pig serum is stated to be present in the form of this blue protein. The copper in serum obtained from pregnant women and from patients with infections and other diseases, like ceruloplasmin, is precipitated by 50 per cent saturation with ammonium sulfate. Furthermore, the ability of serum to oxidize paraphenylene diamine is proportional to the copper content not only in normal serum but also in serum obtained from the umbilical vein, from pregnant womenand from patients with infections (5). Presumably then, in patients with hypercupremia the copper is in the form of ceruloplasmin. The problem still remains as to whether or not ceruloplasmin serves the function of transporting newly absorbed copper from the gastro-intestinal mucosa to the liver. Since the concentration of copper (ceruloplasmin) in normal human serum is relatively constant and is not influenced by meals or by the ingestion of copper (6-8), it seems unlikely that this protein is concerned in the active transport of copper. More important is the observation (1) that the copper in ceruloplasmin does not react directly with sodium diethyldithiocarbamate, whereas copper added to serum in sitro does react directly with this reagent (9). This would indicate that, unlike the ability of serum to

Diurnal Variation in the Plasma Iron Level of Man.

Summary It has been shown that the plasma iron of man undergoes a regular diurnal variation. These results have been compared with those of other investigators.

THE ANEMIA OF INFECTION. XIV. RESPONSE TO MASSIVE DOSES OF INTRAVENOUSLY ADMINISTERED SACCHARATED OXIDE OF IRON

The anemia of infection is associated with a number of alterations in iron metabolism. Previous studies (1-4) have shown that, with the development of inflammation, hypoferremia occurs and a decrease takes place in the concentration of the metal binding protein in the plasma. When iron is given by mouth, there is little change in the level of plasma iron and, following the intravenous injection of iron, only a transient rise in the plasma iron develops. These findings have suggested that diversion of iron from the plasma takes place in inflammation and infection. Studies in experimental animals have shown that iron is diverted primarily to the liver and spleen. Whether this iron is simply stored, since less can be used in the face of diminished hemoglobin production, or performs a special function in connection with the presence of inflammation, is unknown. These findings contrast with those associated

Uric Acid Metabolism in Hepatolenticular Degeneration.

Summary It has been found that in patients with hepatolenticular degeneration (Wilsons disease) the level of uric acid in the serum is reduced and the amount of uric acid excreted in the urine is increased. Following the intravenous administration of uric acid, such patients excrete uric acid in the urine more rapidly than do normal subjects. No correlation was observed between the excretion of copper and that of uric acid. It is suggested that the alterations in uric acid metabolism are due to an inability of the renal tubules to reabsorb uric acid efficiently.

Studies on Copper Metabolism. XXVI. Plasma Copper in Patients with Tropical Sprue.

Summary 1. Plasma copper was determined in 29 patients with sprue in relapse, 27 patients with sprue in remission, and 6 patients with megaloblastic anemia of pregnancy. 2. Mean plasma copper concentration (± 1 S.D.) in patients with sprue in relapse was 87 ± 33 μg%; in treated patients, 114 ± 33; and in patients with megaloblastic anemia of pregnancy, 159 (105 − 242). 3. It is suggested that hypocupremia in sprue may frequently be due primarily to an inability to synthesize the protein portion of ceruloplasmin. In a few patients malabsorption of copper may be a contributing factor.

Copper metabolism. XII. Influence of manganese on metabolism of copper.

Summary 1. Administration of large amounts of manganese to rats was associated with an increase in the concentration of copper in plasma and brain, a decrease in the urinary excretion of copper, a decrease in the concentration of copper in the kidneys, no alteration in the concentration of copper in the liver, and microcytic, hypochromic anemia. The total amount of copper in the body was not increased. 2. Administration of large amounts of copper was accompanied by an increase in total body copper and an increase in the concentration of copper in the plasma, urine, liver, and kidneys but not in the brain. Anemia did not occur. 3. Simultaneous administration of large amounts of both manganese and copper resulted in a marked increase in total body copper, an increase in the concentration of copper in the plasma, liver, kidneys and brain, and microcytic, hypochromic anemia. The total amount of copper in the body of these animals was twice as great as in rats given the same amount of supplemental copper alone. The concentration of copper (μg/100 g of body weight) was increased 5-fold. 4. It is suggested that manganese may form a complex with copper which makes the latter unavailable or that in some manner it blocks the action of copper-containing enzymes.

Studies on copper metabolism. V. Storage of iron in liver of copper-deficient rats.

Summary No alteration from the normal in the uptake of parenterally administered radioiron into the saline-soluble and saline-insoluble fractions of liver iron was observed in copper-deficient albino rats.

Anemia of infection. XVIII. Effects of turpentine and colloidal thorium dioxide on rat plasma iron levels.

Summary Single intravenous injections of colloidal thorium dioxide in the rat produced a marked transient hypoferremia. A more persistent hypoferremia resulted from the administration of this substance daily for 3 days both in intact and in splenectomized rats. The hypoferremia producing effect of turpentine was markedly decreased by the prior administration of colloidal thorium dioxide.