Role of copper transporters in copper homeostasis.

Abstract

Copper is a redox active metal that is essential for biological function. Copper is potentially toxic; thus, its homeostasis is carefully regulated through a system of protein transporters. Copper is taken up across the lumen surface of the small intestinal microvilli as cuprous ion by Ctr1. Cupric ion may also be taken up, but those processes are less well understood. Within the cell, intestinal as well as others, copper is escorted to specific compartments by metallochaperones. One, CCS, donates copper to superoxide dismutase. Another, COX17, delivers copper to additional chaperones within the mitochondria for synthesis of cytochrome c oxidase. A third chaperone, Atox1, delivers copper to the secretory pathway by docking with 2 P-type ATPases. One, ATP7A, is the protein nonfunctional in Menkes disease. This protein is required for cuproenzyme biosynthesis, and in the enterocyte it is required for copper efflux to portal blood. The second, ATP7B, predominantly expressed in liver, is required for copper metallation of ceruloplasmin and biliary copper excretion. Mutations in ATP7B lead to Wilson disease. Additional intracellular hepatic copper-binding proteins COMMD1 (copper metabolism MURR1 domain) and XIAP (X-linked inhibitor of apoptosis protein) may also be required for excretion. Other proteins involved in copper homeostasis may include metallothionein and amyloid precursor protein. Plasma protein transport of copper from the intestine to liver and in systemic circulation probably includes both albumin and alpha2-macroglobulin. Changes in the expression of copper "transporters" may be useful to monitor copper status of humans, provided a suitable cell type can be sampled.

• Authors: Joseph R Prohaska
• Journal: The American journal of clinical nutrition (Am J Clin Nutr) Vol. 88 Issue 3 Pg. 826S-9S (Sep 2008) ISSN: 1938-3207 [Electronic] United States
• PMID: 18779302 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cation Transport Proteins
• Copper Transporter 1
• Molecular Chaperones
• SLC31A1 protein, human
• Copper
• Adenosine Triphosphatases

Topics

• Adenosine Triphosphatases (metabolism)
• Cation Transport Proteins (metabolism)
• Copper (metabolism)
• Copper Transporter 1
• Homeostasis
• Humans
• Molecular Chaperones (metabolism)