Studies on the Function and Metabolism of Copper

Abstract
Copper is found in blood in the plasma and in the cells. Red cell copper tends to be constant. The plasma copper, on the other hand, increases under a great variety of circum-stances. Hypocupremia is rare. By far the greatest proportion of plasma copper is in the form of a copper protein corresponding to an α-globulin. A very small part of plasma copper is bound more loosely to one of several possible protein fractions and may represent copper in transit. Deficiency of copper is associated with the development of severe, hypochromic microcytic anemia, hypoferremia as well as hypocupremia, moderate leukopenia and bone marrow normoblastic hyperplasia. In copper-deficient swine fed ample amounts of iron, the total body content of iron, as measured by chemical assay of the tissues or by measurement of radioactive iron, is low as compared with normal. Copper therapy without the simultaneous administration of iron in such animals is ineffective. In swine made deficient both in copper and iron, no increase in plasma iron follows iron therapy but an increase takes place promptly when copper is given as well. These observations are interpreted as indicating that copper favors iron absorption from the gastrointestinal tract. That copper is also concerned in the mobilization of iron from the tissues is suggested by several observations. Thus, analysis of the iron content of copper-deficient animals reveals that the chief depletion of total body iron is in the hemoglobin compartment. This suggests that movement of iron from the tissues to the plasma is decreased. This view is also supported by the observation that in copper-deficient swine the administration of copper is followed by a very sharp rise in the plasma iron content. That impaired utilization of iron for hemoglobin synthesis is another factor in the disturbed iron metabolism of copper deficiency is indicated by the fact that the intravenous or intraperitoneal administration of iron fails to relieve the anemia in copper-deficient animals. Furthermore, studies with intravenously-administered radioactive iron reveal that the uptake of iron for hemoglobin synthesis is poor in copper-deficient swine.