Plasma copper

Caeruloplasmin (Cp) is an acute phase glycoprotein with a copper transport function. At least 90% of total plasma copper is bound to Cp with the remaining 10% associated with albumin, histidine and small peptides. Lipid peroxidation requires the presence of trace amounts of transition metals and the copper-containing active site of Cp endows it with antioxidant capacity... 

Sutton AM, Harvie A, Cockburn F, Farquharson J, Logan RW (1985) Copper defidency in preterm infants of very low birthweight. Four cases and a reference range for plasma copper. Arch Dis Childh 60 644-651. 

Adults require 1-2 mg of copper per day, and eliminate excess copper in bile and feces. Most plasma copper is present in ceruloplasmin. In Wilson s disease, the diminished availability of ceruloplasmin interferes with the function of enzymes that rely on ceruloplasmin as a copper donor (e.g. cytochrome oxidase, tyrosinase and superoxide dismutase). In addition, loss of copper-binding capacity in the serum leads to copper deposition in liver, brain and other organs, resulting in tissue damage. The mechanisms of toxicity are not fully understood, but may involve the formation of hydroxyl radicals via the Fenton reaction, which, in turn initiates a cascade of cellular cytotoxic events, including mitochondrial dysfunction, lipid peroxidation, disruption of calcium ion homeostasis, and cell death. 

Single intravenous injection of 80 (jg/kg BW juveniles, 100-300 g in body weight Half-time persistence in plasma was 7.2 min for the short-lived component and 3.2 h for the long-lived component. Plasma copper concentration fell from 1.1 mg/L shortly after administration to about 200 pg/L after 7.5 h 137... 

Auer, D.E., J.C. Ng, D.P. Steele, and A.A. Seawright. 1988b. Monthly variation in the plasma copper and zinc concentration of pregnant and non-pregnant mares. Austral. Veterin. Jour. 65 61-62. 

Reduction of 30% in milk yield rapid decline in plasma copper milk Mo levels of 1.6 mg/L growth reduction in nursing calves (6) Low liver copper, intestinal disturbances, brittle bones prone to fracture (7)... 

In 5-week-old calves, there was no effect on liver or plasma copper levels (9)... 

Animals remained healthy. No decline in total plasma copper or increase in plasma insoluble copper (14)... 

No effect on growth of food intake significant increases in levels of kidney cortex copper, liver Mo, and plasma copper major differences in responses among breeds tested (21)... 

During pregnancy (40th week) the level averages about 260 ig. per cent. The fact that the plasma copper level is altered by numerous conditions mentioned above is ample evidence of its physiological significance. A large part of the copper of the plasma is combined to produce a specific protein which has been called coeruloplasmin. 16... 

In recent history, the therapeutic potential for copper in the treatment of rheumatic diseases was recognized by Hangartner in 1939 when he learned that copper miners in Finland were free of rheumatism. Sorenson25 has reviewed the literature on changes in copper concentrations in patients with rheumatoid arthritis. In patients with active disease there are marked increases in serum or plasma copper, an accelerated turnover rate of ceruloplasmin, and an increase of synovial fluid copper. A number of copper-dependent enzymes are known to be required for repair of inflamed tissues. 

Thrombin (MW 39,000) is a proteolytic enzyme of the serine protease group. It is derived from prothrombin, a circulating plasma protein, through the proteolytic action of a complex consisting of the proteolytic enzyme factor X (or factor Xa), another protein called factor V (accelerator protein), calcium, and phospholipid. Factor V has recently been identified as the plasma copper protein ceruloplasmin or a similar protein (see Chapter 6). 

Table II. Comparison of Plasma Zinc and Plasma Copper Concentrations Between Epileptics and Age, Sex, Race and Height/Weight Ratio Matched Controls...

Ceruloplasmin is an enzyme synthesised in the liver which contains six atoms of copper in its structure. Ceruloplasmin carries 90% of plasma copper the other 10% is carried by albumin. Ceruloplasmin exhibits a copper-dependent oxidase activity, which is associated with possible oxidation of Fe + (ferrous iron) into Fe (ferric iron), therefore assisting in its transport in the plasma in association with transferrin, which can only carry iron in the ferric state. 

Much of the copper in the plasma (60-95%) is bound to ceruloplasmin. The complex of copper and cenjloplasmir is assembled and secreted by the liver. A small fraction of plasma copper, under 7%, is weakly bound to albumin and to free amino acids, especially histidine, threonine, and glutamine. The copper bound to serum albumin is associated with a histidine residue near the amino terminus of the protein. The copper in red blood cells is bound to superoxide dismutase. 

A 17-year-old man developed fatigue after taking large daily doses of zinc supplements for 6-7 months in an attempt to treat his acne (7). He initially took 50 mg/ day, but because his acne did not improve he increased the dosage to 100 mg tds. He had anemia and neutropenia. His plasma zinc concentration was 1.95 (reference range 0.50-0.95) pg/ml 1 month after withdrawal and 1.69 pg/ml 1 month later. His plasma copper concentration was 0.12 (reference value 0.90-2.35) pg/ml. When his anemia and neutropenia had resolved 4 months later, the zinc and copper concentrations had returned to normal. 

The genetic syndrome referred to as Menkes kinky hair has been studied by Williams et al. (73). No changes were observed following oral copper supplementation in plasma copper concentration or ceruloplasmin concentration in these patients. However, when copper was given intravenously, a rise in ceruloplasmin was seen. The results indicate that in Menkes syndrome, there is a defect in copper-binding protein which leads to excessive losses of copper from the gastrointestinal tract. 

Based on reports by other workers in this field and on our own findings, two hypotheses could be postulated to explain the increased serum copper concentration with age. Since tissues in these subjects were not examined for copper concentrations, increased serum copper concentration may either represent an increase in the total body pool of copper or, alternatively, the copper may have shifted from another organ, thus increasing plasma copper, plasma in this instance acting as a vehicle for transiently transporting the metal to other parts of the body where it is needed. 

The incidence of Wilson s disease is estimated to be 1/30,000 live births with a carrier frequency of 1/90 in the general population. The presentation is highly variable, so adolescents or young adults with otherwise unexplained liver disease or neurological symptoms should be screened, especially where there is a family history of suspected Wilson s disease. Initial local investigations would include plasma copper and ceruloplasmin, which will usually be low (less than 50 Llg/dL, 8 [imol Cu per L, and less than 200 mg/L ceruloplasmin). Although the total plasma copper is decreased, the nonceruloplasmin bound fraction is increased, allowing deposition of copper in the brain, eyes, and kidneys. 

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