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copper-transport diseases

Thursday 22 April 2004

Definition: Copper is an element essential for life, but excessive copper can be toxic or even lethal to the cell. Therefore, cells have developed sophisticated ways to maintain a critical copper balance, with the intake, export, and intracellular compartmentalization or buffering of copper strictly regulated.

The 2 related genes ATP7A (MIM.300011) and ATP7B (MIM.606882), responsible for the human diseases Menkes syndrome (MIM.309400) and Wilson disease (MIM.277900), respectively, are involved in copper export.

In S. cerevisiae, the copper uptake genes CTR1, CTR2, and CTR3 have been identified, and in human the CTR1 and CTR2 (MIM.603088) genes have been identified.

Pathways of copper trafficking within a mammalian cell.

The three principle copper chaperones are Cox17, CCS and Atox1. Their respective protein targets are cytochrome c oxidase, SOD1 and the Wilson and Menkes copper transporting ATPases.

The mechanisms regulating initial copper uptake into the cell via the membrane transporter Ctr1 and the subsequent distribution of this metal to each chaperone remain unknown.


- Menkes disease (copper deficiency)
- Wilson disease (copper toxicosis)


Menkes disease and Wilson disease are two human genetic disorders caused by mutations of two closely related Cu-transporting ATPases. Both molecules efflux copper from cells (Cu-transporting proteins).


- Madsen E, Gitlin JD. Copper and iron disorders of the brain. Annu Rev Neurosci. 2007;30:317-37. PMID: 17367269

- Mercer JF. The molecular basis of copper-transport diseases. Trends Mol Med. 2001 Feb;7(2):64-9. PMID: 11286757