35 percent of a 2 mg/day intake is absorbed and is transported via the portal vein to the liver, bound to albumin, for uptake by liver parenchymal cells.
Biliary copper excretion is adjusted to maintain balance. Copper is released via plasma to extrahepatic sites where up to 95 percent of the copper is bound to ceruloplasmin (Turnlund, 1999). The biological role of ceruloplasmin in copper metabolism has been widely investigated. The autosomal recessive disorder in humans, aceruloplasminemia, does not produce abnormal copper metabolism, thus contradicting a role for the protein in copper delivery to cells. However, this genetic defect results in tissue iron accumulation, supporting the protein’s role in cellular iron release. Other P-type ATPases (e.g., Wilson, NND, ATP7B) are responsible for copper trafficking to the secretory pathway for ceruloplasmin synthesis or for endosome formation before transport into the bile (Harris and Gitlin, 1996; Pena et al., 1999). Mutations of this copper-transporting ATPase result in cellular copper accumulation called Wilson’s disease. Urinary copper excretion is normally very low (< 0.1 mg/day) over a wide range of dietary intakes (Turnlund, 1999). As with other trace elements, renal dysfunction can lead to increased urinary losses.
Frank copper deficiency in humans is rare, but has been found in a number of special conditions. It has been observed in premature infants fed milk formulas, in infants recovering from malnutrition associated with chronic diarrhea and fed cow’s milk (Shaw, 1992), and in patients with prolonged total parenteral nutrition (Fujita et al., 1989). In these cases, serum copper and ceruloplasmin concentrations were as low as 0.5 μmol and 35 mg/L, respectively, compared to reported normal ranges of 10 to 25 μmol/L for serum copper concentration and 180 to 400 mg/L for ceruloplasmin concentration (Lentner, 1984). Supplementation with copper resulted in rapid increases in serum copper and ceruloplasmin concentrations.
Symptoms accompanying the copper deficiency included normocytic, hypochromic anemia, leukopenia, and neutropenia (Fujita et al., 1989). Osteoporosis was observed in copper-deficient infants and growing children.
Copper deficiency developed in six severely handicapped patients between the ages of 4 and 24 years who were fed an enteral diet containing 15 μg of copper/100 kcal for 12 to 66 months (Higuchi