Defective CP does not oxidise Fe2+ to Fe3+

Stable Identifier
R-HSA-5621402
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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. 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.

Mutations that can cause ACERULOP include W858*, E797Rfs*12, D411Tfs*36 and 778fs*12 (Takahashi et al. 1996, Logan et al. 1994, Okamoto et al. 1996, Harris et al. 1995).

Literature References
PubMed ID Title Journal Year
8789443 Characterization of a nonsense mutation in the ceruloplasmin gene resulting in diabetes and neurodegenerative disease

Takahashi, Y, Miyajima, H, Shirabe, S, Nagataki, S, Suenaga, A, Gitlin, JD

Hum. Mol. Genet. 1996
8641692 Hereditary ceruloplasmin deficiency with hemosiderosis

Okamoto, N, Wada, S, Oga, T, Kawabata, Y, Baba, Y, Habu, D, Takeda, Z, Wada, Y

Hum. Genet. 1996
7708681 Aceruloplasminemia: molecular characterization of this disorder of iron metabolism

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

Proc. Natl. Acad. Sci. U.S.A. 1995
7820540 Hereditary caeruloplasmin deficiency, dementia and diabetes mellitus

Logan, JI, Harveyson, KB, Wisdom, GB, Hughes, AE, Archbold, GP

QJM 1994
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
ferroxidase activity of CP mutants:6xCu2+:SLC40A1 [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
aceruloplasminemia 0050711
Authored
Reviewed
Created
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