Liver, copper

Marine mammals usually contain less than 44 mg Cu/kg DW in all tissues except livers. Copper in livers seldom exceeds 116 mg/kg DW except in polar bears (146 mg/kg DW), and manatees, Trichechus manatus, (1200 mg/kg DW) from a copper-contaminated site (Table 3.3). Maximum copper concentrations in terrestrial mammals from all collection sites are usually less than 29 mg/kg DW in all tissues except kidneys (108 mg/kg DW) and livers (1078 mg/kg DW Table 3.3). 

Human foods that are particularly rich in copper (20 to 400 mg Cu/kg) include oysters, crustaceans, beef and lamb livers, nuts, dried legumes, dried vine and stone fruits, and cocoa (USEPA 1980). In humans, copper is present in every tissue analyzed (Schroeder et al. 1966). A 70-kg human male usually contains 70 to 120 mg of copper (USEPA 1980). The brain cortex usually contains 18% of the total copper, liver 15%, muscle 33%, and the remainder in other tissues — especially the iris and choroid of the eye. Brain gray matter (cortex) has significantly more copper than white matter (cerebellum) copper tends to increase with increasing age in both cortex and cerebellum. In newborns, liver and spleen contain about 50% of the total body burden of copper (USEPA 1980). Liver copper concentrations were usually elevated in people from areas with soft water (Schroeder et al. 1966). Elevated copper concentrations in human livers are also associated with hepatic disease, tuberculosis, hypertension, pneumonia, senile dementia, rheumatic heart disease, and certain types of cancer (Schroeder et al. 1966). 

Initial inhibition of sodium uptake and whole body sodium content that were normal by day 28. Abnormal liver enzyme activity. Liver copper increased from 23 mg/kg FW at start to 113 mg/kg FW at day 28... 

Strain genetically deficient in copper (Menkes disease) given subcutaneous injections of 50 pg copper chloride (CuCI2) on postnatal days 7 and 10. Before therapy, liver copper concentration was 3.1 mg/kg FW (vs. 30.1 mg/kg FW in normal mice)... 

Postmortem examination of 17 lambs that died suddenly showed brain histopathology, particularly in white matter of midbrain, pons, and cerebellum. Severe liver cirrhosis and necrosis of kidney tubules. Liver copper elevated at 3225 to 4325 mg/kg DW... 

Newly weaned shrews fed diets equivalent to 2.13 mg copper/shrew daily for 12 weeks uncontaminated diets contained 25.1 mg/kg DW ration No effect on growth, survival, or tissue copper burdens kidney and liver copper concentrations increased in response to cadmium dosing 24, 25... 

Growth and fertilization rate normal liver copper >70 mg/kg DW 63% of embryos developed normally (2)... 

Reduced food intake and efficiency of food use, altered iron metabolism, clinical signs of copper deficiency. Onset of puberty delayed 10 weeks, decreased conception rate (fertility 12-33% vs. 57-80% in controls), disrupted estrus cycle (67% were anestrus vs. 7% in controls), and other signs consistent with decreased releases of luteinizing hormones associated with altered ovarian secretion (3, 4) Growth and fertilization normal liver copper 10 mg/kg DW only 16% of embryos developed normally (2)... 

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)... 

Metallothioneins play an important role in the metabolism of copper, both in absorption and handling by the liver. Dietary supplementation with copper leads to a large increase in liver copper-metallothionein. The biological life of metallothionein can vary considerably. The half-life of Cu-metallothionein in zinc-deficient rats (12.3 h) was lower than that in zinc-sufficient rats (16.9 h).1166 Usually zinc is found in Cu-metallothionein, so zinc may stabilize the copper metallothionein.1167... 

Wilson s disease is a copper storage disorder that is apparently due to an inherited lesion in the copper excretion mechanism. One in 200-400 persons is a carrier of the disease. Diagnosis may be made by measuring serum ceruloplasmin levels. Whereas normal serum ceruloplasmin is 200-400 mg/L, in Wilson s disease patients it is well below 200 mg/L. Liver copper in these patients (determined by biopsy) is more than 250 /xg/g, whereas normal individuals show a value of only 20-45 /xg/g. Liver function deterioration is the most prominent symptom of Wilson s disease. Treatment includes chelation therapy with penicillamine. 

Jl. Jewett, S. L., Cushing, S., Gillespie, F., Smith, D., and Sparks, S., Reaction of bovine-liver copper-zinc superoxide dismutase with hydrogen peroxide. Evidence for reaction with H2O2 and HOj leading to loss of copper. Eur. J. Biochem. 180, 569-575 (1989). 

Liver copper levels (Liver copper levels... 

Wilson s disease often involves low plasma levels of ceruloplasmin, increased plasma nonceruloplasmin copper, and increased urinary copper. The disease can involve a tenfold increase in liver copper lev els. The normal value for hepatic copper is 20 to 50 pg/g of liver dry weight). Outward signs of the disease include episodes of jaundice, vomidng, and tiredness. Bone disorders such as osteoporosis can also occur. The neurological damage includes a loss in coordination. V ilson s disease does not result in mental retardation. The rate of incorporation of copper into ceruloplasmin is reduced and biliary excretion decreases to 20 to 40% the normal rate. 

Many of these copper proteins are enzymes, and the copper is a part of their active group (Nos. 1, 10-14 in Table 4), while others have no known enzyme activity (Nos. 2-9). As far as is known, none of these proteins functions as a respiratory carrier, as hemocyanin does in mollusks. It has been suggested, but not proven, that the human liver copper protein of Morell et al. (M32) and the hepatic mitochondrocuprein of Porter et al. (P13, P15) may function as copper storage proteins, similar perhaps to ferritin in the case of iron. 

It may be questioned whether all these proteins are separate entities. There are many similarities between hemocuprein and erythrocupiein, and also between hepatocuprein, horse liver copper protein, and human hepato-cuprein. Porter suggested that the erythrocuprein of Markowitz et al. (P14), cerebrocuprein I, and human hepatocuprein may be identical proteins, although he recognizes some differences between them. 

The copper in some of these copper proteins accounts for a sizable portion or all of the copper present in the organ compartment where they are found. Copper locked in ceruloplasmin accounts for 90-95% of the copper in plasma (H14). Copper boimd to human liver copper protein, according to Morell, accounts for as much as 80% of the total copper in the sub-cellular soluble fraction of liver (M32), and another 7% is accounted for... 

The high tissue copper levels of the newborn decrease soon after birth. In three infants between 3 and 12 months of age Nusbaum et al. (N7) found the copper content of the liver and kidney to be within the normal adult range. On the other hand, Gerlach (Gl) found high liver copper content in some infants up to 1 year of age. In children between 7 and 13 years of age the tissue copper concentrations were not different from those in adults (Gl, S9). 

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