Copper

  • Copper (Cu) is a trace element found in all body organs; the highest percentage being in muscle. It forms part of the catalytic site of several enzymes such as superoxide dismutase (SOD), amino acid oxidases and mitochondrial cytochrome c oxidase (for a detailed description of mitochondrial Fe-Cu cytochrome c oxidase see ref. 1).
  • Required for the crosslinking of collagen and elastin (proteins found in the blood vessel walls and responsible for their mechanical resistance) by the copper enzyme lysyl oxidase (2). Poor collagen integrity may lead to blood vessel fragility, osteoporosis and joint dysfunction.
  • Disruption of normal Cu homeostasis can lead to severe medical conditions such as Wilson's disease and Menkes disease. The latter is a fatal childhood neurodegenerative disorder caused by a mutation in a gene (on the X chromosome) encoding a Cu-transporting ATPase; patients afflicted by this condition exhibit symptoms of Cu deficiency. It has been recently shown that the Cu transporter ATPase functions by carrying Cu from a N-methyl-D-aspartate receptor-dependent releasable pool of Cu in hippocampal neurons (3). It was suggested that the neuronal degeneration may result from impaired Cu homeostasis brought about by an impairment of Cu efflux from its storage site.
  • In the liver cells Cu is transported by chaperone proteins such as Cu-ATPase, which directs Cu to either ceruloplasmin for export or within the trans Golgi network to the proteins a amidating monooxygenase, lysyl oxidase, tyrosinase, dopamine b monooxygenase. Another chaperone delivers Cu to the mitochondrial cytochrome c oxidase (4,5). The so-called Menkes ATPase has been also shown to transport Cu to a secretory superoxide dismutase (SOD3) in the trans Golgi network of vascular cells (6).
  • Metallothioneins are another class of proteins involved in Cu homeostasis. They function as an important storage protein for Cu as well as for zinc (7).
  • Involved, as part of the copper carrier protein ceruloplasmin and the superoxide dismutase in free radical scavenging activity. The cytosolic SOD contains Cu2+ and Zn2+ in the catalytic site while the mitochondrial SOD contains Mn2+.
  • Takes part as enzyme cofactor in processes such as energy production (in cytochrome c oxidase), skin pigment melanin (in tyrosinase), amino acid metabolism (in amino acid oxidases).
  • Interactions: A high intake of vitamin C, zinc and iron may impair the absorption of copper.
  • Health benefits: Supplementation is not recommended if a diet rich in shellfish or nuts is consumed. An adequate level of copper in body tissues may prevent cardiovascular disease and arthritis.
  • Best food sources: Oysters and other shellfish, nuts.


References
1. Lehninger Principles of Biochemistry, D.L. Nelson and M.M. Cox, W.H. Freeman & Co. New York,
    p.702, 2005.
2. Szauter, K.M. et al. (2005) Pathol.Biol.(Paris) 53(7) 448-456. Lysyl oxidase in development, aging and
    pathologies of the skin.
3. Schlief, M.L. et al. (2006) Proc.Natl.Acad.Sci.USA 103(40) 14919-14924. Role of the Menkes copper-
    transporting ATPase in NMDA receptor-mediated neuronal toxicity.
4. Prohaska, J.R. & Gybina, A.A. (2004) J.Nutr. 134(5) 1003-1006. Intracellular copper transport in
    mammals.
5. Lutsenko, S. & Petris, M.J. (2003) J.Membr.Biol. 191(1) 1-12. Function and regulation of the
    mammalian copper-transporting ATPases: insights from biochemical and cell biological approaches.
6. Qin, Z. et al. (2006) FASEB J. 20(2) 334-336. Essential role for the Menkes ATPase in activation of
    extracellular supeeroxide dismutase: implication for vascular oxidative stress.
7. Cai, L. et al. (2005) Curr.Med.Chem. 12(23) 2753-2763. Essentiality, toxicology and chelation therapy
    of zinc and copper.