Blood coagulation Ferroxidase activity
Factors V and VIII
The common feature of reactions catalyzed by cuproenzymes is the involvement of molecular oxygen or a derivative; thus, unlike the metalloenzymes of zinc, cuproenzymes almost universally govern the rate-limiting steps in the respective biochemical pathways. Therefore, unlike zinc, most of the clinical expression of copper deficiency in humans (except for the hematological manifestations) can be explained on a molecular basis in terms of the deficiency of one or another metalloenzyme of copper.77
Dietary copper bioavailability (40 to 60%) can be affected by other nutrients and the status of its primary binding protein, ceruloplasmin. Copper stores (approximately 120 mg) are mainly in the liver and are secreted in saliva, gastric and pancreatic juice, and bile. A copper-metallothionein complex present in intestinal mucosal cells is shed into the intestinal lumen.
Medications such as estrogen stimulate ceruloplasmin and therefore increase mean serum copper concentrations in females. Even higher serum coppers are found in women who are pregnant (during the third trimester), in patients with hyperthy-roidism, and in those using oral contraceptives.78 Copper and ceruloplasmin concentrations are also higher in those who smoke and in those with conditions involving chronic inflammation (e.g., rheumatoid arthritis), chronic infection, and some neoplasms. Serum copper concentrations in patients with burns over 15% of their bodies remain within normal limits, and hypozincemia was found in patients irrespective of burn surface area. Long-term monitoring of patients with burns over 70% of their bodies shows initial hypocupremia and hypozincemia.79
Although typically bound to proteins, copper may be released and become free to catalyze the formation of highly reactive hydroxyl radicals. Data obtained from in vitro and cell culture studies are largely supportive of copper's capacity to initiate oxidative damage and interfere with important cellular events. Oxidative damage has been linked to chronic copper overload and exposure to excess copper caused by accidents, occupational hazards, and environmental contamination. Additionally,
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