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Copper (Cu), an essential trace element, is required for the survival of organisms
ranging from bacteria to mammals. Because Cu ions can adopt distinct redox states (oxidized
Cu[II] or reduced Cu[I]), they play a pivotal role in cell physiology as catalytic
cofactors in the redox chemistry of enzymes involved in a broad spectrum of biological
activities. For example, copper is an important cofactor in mitochondrial respiration, iron
absorption, collagen and elastin crosslinking, and free radical scavenging.
Copper balance studies in volunteer human subjects have indicated a minimum requirement
of 1.5 –2.0 mg per diem. Therefore, the RDA (Recommended Dietary Allowances) has
been set at 2–3 mg per diem. In the United States, the average daily intake of Cu is approx
1 mg and diet is the primary source. The bioavailability of Cu from the diet is about 65–70%
depending on a variety of factors including its chemical form and interaction with other
metals and dietary components. Although ingested Cu is readily absorbed, little excess is
stored. Therefore, it is both noteworthy and puzzling that symptoms of Cu deficiency have
not been identified in the general population. However, the biological half-life of dietary Cu
is 13–33 d with biliary excretion being the major route of elimination. In healthy persons,
serum Cu concentrations range up to approx 1.5 mg/L. Gastrointestinal symptoms occur at
whole blood concentrations near 3.0 mg Cu/L.
It is well known that Cu plays a fundamental role in the biochemistry of the human
nervous system. The dramatic neurodegenerative phenotypes of Menkes and Wilson
diseases underscore the essential nature of this metal in nervous system development and
the consequences of perturbation of neuronal Cu homeostasis. In addition, inherited loss
of ceruloplasmin, an essential ferroxidase contains 95% of the Cu found in human plasma,
is associated with progressive neurodegeneration of the retina and basal ganglia. Recent
studies also have implicated Cu in the pathogenesis of neuronal injury in Alzheimer's
disease and the prion-mediated encephalopathies, suggesting that further elucidation of
the mechanisms of Cu trafficking and metabolism within the nervous system will be of direct
relevance to understanding the pathophysiology and treatment of some neurodegenerative
diseases. |
