The Identification of Motifs Involved in the Intracellular Trafficking of the Menkes Disease Protein
Year: 2002
Type: book-chapter
Abstract: Menkes disease is a severe neurodegenerative disorder arising from a defect in copper transport. The incidence of this disease has been estimated at 1 in 250,000 (1), although in some populations it can be as high as 1 in 40,000 (2). A less severe form of the disease, occipital horn syndrome (OHS) or X-cutis laxis, resulting from an allelic variant, has also been described. The clinical symptoms of both Menkes disease and OHS are caused by a lack of serum copper and copper-requiring enzymes, such as lysyl oxidase and cytochrome-c oxidase. In normal individuals, dietary copper is taken into the body and the majority is absorbed by the stomach and the small intestine. The copper is transported primarily with ceruloplasmin and is complexed to histidine and albumin. The copper is reduced to Cu(I) and taken up into the cell. In patients with Menkes disease, absorption of orally administered copper is much reduced, and the brain, blood, and liver show decreased levels of copper. However, in many other tissues, there is an increase in copper levels when compared to normal individuals, although there is still a defect in the function of copper-requiring enzymes (3). Cultured fibroblasts from patients show both an excess accumulation of copper and efflux abnormalities from these cells (4–7). These results suggest that the protein responsible for Menkes disease has a direct role in the intracellular transport of copper. This chapter discusses the role of motifs within the Menkes disease protein involved in this transport.
Source: Humana Press eBooks
Authors: Michael J. Francis, Anthony P. Monaco
Language: English
Topic: Trace Elements in Health
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W2264225279