Defective CP causes aceruloplasminemia (ACERULOP)

Stable Identifier
Homo sapiens
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Ceruloplasmin (CP), synthesised in the liver and secreted into plasma, is a copper-binding (6-7 atoms per molecule) glycoprotein involved in iron trafficking in vertebrates. CP is essential for SLC40A1 (ferroportin) stability at the cell surface, the protein that mediates iron efflux from cells. CP also possesses ferroxidase activity, which oxidises ferrous iron (Fe2+) to ferric iron (Fe3+) following its transfer out of the cell. Fe3+ can then be loaded on to extracellular transferrin which transports it around the body to sites where it is required. Iron is vital for many metabolic processes such as electron transport and the transport and storage of oxygen.

Defects in CP (or indeed SLC40A1) can lead to the phenotype of iron overload as seen in the disorder aceruloplasminemia (ACERULOP; MIM:604290). It is a rare autosomal recessive disorder of iron metabolism characterised by iron accumulation mainly in the brain, but also in liver, pancreas and retina. Patients develop retinal degeneration, diabetes mellitus and neurological disturbance. ACERULOP belongs to a group of disorders known as NBIA (neurodegeneration with brain iron accumulation), distinguishing it from hereditary hemochromatosis (serum iron is high but the brain is usually not affected) and from disorders of copper metabolism such as Menkes and Wilson disease (Harris et al. 1995, Kono 2012, Musci et al. 2014).
Literature References
PubMed ID Title Journal Year
24921009 Ceruloplasmin-ferroportin system of iron traffic in vertebrates

Polticelli, F, Musci, G, Bonaccorsi di Patti, MC

World J Biol Chem 2014
7708681 Aceruloplasminemia: molecular characterization of this disorder of iron metabolism

Gitlin, JD, Takahashi, Y, Serizawa, M, Harris, ZL, MacGillivray, RT, Miyajima, H

Proc. Natl. Acad. Sci. U.S.A. 1995
22515740 Aceruloplasminemia

Kono, S

Curr Drug Targets 2012
Name Identifier Synonyms
aceruloplasminemia DOID:0050711
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