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Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948.4 Another protein, hephaestin, is noted for its homology to ceruloplasmin, and also participates in iron and probably copper metabolism.
Ceruloplasmin is an enzyme (EC188.8.131.52) synthesized in the liver containing 6 atoms of copper in its structure.5 Ceruloplasmin carries more than 95% of the total copper in healthy human plasma.6 The rest is accounted for by macroglobulins. Ceruloplasmin exhibits a copper-dependent oxidase activity, which is associated with possible oxidation of Fe2+ (ferrous iron) into Fe3+ (ferric iron), therefore assisting in its transport in the plasma in association with transferrin, which can carry iron only in the ferric state. The molecular weight of human ceruloplasmin is reported to be 151kDa.
A cis-regulatory element called the GAIT element is involved in the selective translational silencing of the Ceruloplasmin transcript.7 The silencing requires binding of a cytosolic inhibitor complex called IFN-gamma-activated inhibitor of translation (GAIT) to the GAIT element.8
Like any other plasma protein, levels drop in patients with hepatic disease due to reduced synthesizing capabilities.
Copper availability doesn't affect the translation of the nascent protein. However, the apoenzyme without copper is unstable. Apoceruloplasmin is largely degraded intracellularly in the hepatocyte and the small amount that is released has a short circulation half life of 5 hours as compared to the 5.5 days for the holo-ceruloplasmin.
Mutations in the ceruloplasmin gene (CP), which are very rare, can lead to the genetic disease aceruloplasminemia, characterized by hyperferritinemia with iron overload. In the brain, this iron overload may lead to characteristic neurologic signs and symptoms, such as cerebellar ataxia, progressive dementia, and extrapyramidal signs. Excess iron may also deposit in the liver, pancreas, and retina, leading to cirrhosis, endocrine abnormalities, and loss of vision, respectively.
Lower-than-normal ceruloplasmin levels may indicate the following:
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^Holmberg CG, Laurell C-B (1948). "Investigations in serum copper. II. Isolation of the Copper containing protein, and a description of its properties". Acta Chem Scand2: 550–56. doi:10.3891/acta.chem.scand.02-0550.
^Sampath P, Mazumder B, Seshadri V, Fox PL (March 2003). "Transcript-selective translational silencing by gamma interferon is directed by a novel structural element in the ceruloplasmin mRNA 3' untranslated region". Mol. Cell. Biol.23 (5): 1509–19. doi:10.1128/MCB.23.5.1509-1519.2003. PMC151701. PMID12588972.
^Mazumder B, Sampath P, Fox PL (October 2005). "Regulation of macrophage ceruloplasmin gene expression: one paradigm of 3'-UTR-mediated translational control". Mol. Cells20 (2): 167–72. PMID16267389.
^Ziakas A, Gavrilidis S, Souliou E, Giannoglou G, Stiliadis I, Karvounis H, Efthimiadis G, Mochlas S, Vayona MA, Hatzitolios A, Savopoulos C, Pidonia I, Parharidis G (2009). "Ceruloplasmin is a better predictor of the long-term prognosis compared with fibrinogen, CRP, and IL-6 in patients with severe unstable angina". Angiology60 (1): 50–9. doi:10.1177/0003319708314249. PMID18388036.
^Lutsenko S, Gupta A, Burkhead JL, Zuzel V (August 2008). "Cellular multitasking: the dual role of human Cu-ATPases in cofactor delivery and intracellular copper balance". Arch. Biochem. Biophys.476 (1): 22–32. doi:10.1016/j.abb.2008.05.005. PMC2556376. PMID18534184.
^Virit O, Selek S, Bulut M, Savas HA, Celik H, Erel O, Herken H (2008). "High ceruloplasmin levels are associated with obsessive compulsive disorder: a case control study". Behav Brain Funct4: 52. doi:10.1186/1744-9081-4-52. PMC2596773. PMID19017404.
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