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RefSeq (mRNA)



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Ceruloplasmin (or caeruloplasmin) is a ferroxidase enzyme that in humans is encoded by the CP gene.[1][2][3]

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 (EC 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.[7] 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.[8] The silencing requires binding of a cytosolic inhibitor complex called IFN-gamma-activated inhibitor of translation (GAIT) to the GAIT element.[9]

Clinical significance

Like any other plasma protein, levels drop in patients with hepatic disease due to reduced synthesizing capabilities.

Mechanisms of low ceruloplasmin levels:

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:


Greater-than-normal ceruloplasmin levels may indicate or be noticed in:

Reference ranges

Normal blood concentration of ceruloplasmin in humans is 20-50 mg/dL.

File:Blood values sorted by mass and molar concentration.png
Reference ranges for blood tests, comparing blood content of ceruloplasmin (shown in gray) with other constituents.


  1. Takahashi N, Ortel TL, Putnam FW (Jan 1984). "Single-chain structure of human ceruloplasmin: the complete amino acid sequence of the whole molecule". Proceedings of the National Academy of Sciences of the United States of America. 81 (2): 390–4. doi:10.1073/pnas.81.2.390. PMC 344682. PMID 6582496.
  2. Koschinsky ML, Funk WD, van Oost BA, MacGillivray RT (Jul 1986). "Complete cDNA sequence of human preceruloplasmin". Proceedings of the National Academy of Sciences of the United States of America. 83 (14): 5086–90. doi:10.1073/pnas.83.14.5086. PMC 323895. PMID 2873574.
  3. Royle NJ, Irwin DM, Koschinsky ML, MacGillivray RT, Hamerton JL (May 1987). "Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively". Somatic Cell and Molecular Genetics. 13 (3): 285–92. doi:10.1007/BF01535211. PMID 3474786.
  4. Holmberg CG, Laurell CB (1948). "Investigations in serum copper. II. Isolation of the Copper containing protein, and a description of its properties". Acta Chem Scand. 2: 550–56. doi:10.3891/acta.chem.scand.02-0550.
  5. O'Brien PJ, Bruce WR (2009). Endogenous Toxins: Targets for Disease Treatment and Prevention, 2 Volume Set. John Wiley & Sons. pp. 405–6. ISBN 978-3-527-32363-0.
  6. Hellman NE, Gitlin JD (2002). "Ceruloplasmin metabolism and function". Annual Review of Nutrition. 22: 439–58. doi:10.1146/annurev.nutr.22.012502.114457. PMID 12055353.
  7. Song D, Dunaief JL (2013). "Retinal iron homeostasis in health and disease". Frontiers in Aging Neuroscience. 5: 24. doi:10.3389/fnagi.2013.00024. PMC 3695389. PMID 23825457.
  8. Sampath P, Mazumder B, Seshadri V, Fox PL (Mar 2003). "Transcript-selective translational silencing by gamma interferon is directed by a novel structural element in the ceruloplasmin mRNA 3' untranslated region". Molecular and Cellular Biology. 23 (5): 1509–19. doi:10.1128/MCB.23.5.1509-1519.2003. PMC 151701. PMID 12588972.
  9. Mazumder B, Sampath P, Fox PL (Oct 2005). "Regulation of macrophage ceruloplasmin gene expression: one paradigm of 3'-UTR-mediated translational control". Molecules and Cells. 20 (2): 167–72. PMID 16267389.
  10. Scheinberg IH, Gitlin D (Oct 1952). "Deficiency of ceruloplasmin in patients with hepatolenticular degeneration (Wilson's disease)". Science. 116 (3018): 484–5. doi:10.1126/science.116.3018.484. PMID 12994898.
  11. Gitlin JD (Sep 1998). "Aceruloplasminemia". Pediatric Research. 44 (3): 271–6. doi:10.1203/00006450-199809000-00001. PMID 9727700.
  12. Elkassabany NM, Meny GM, Doria RR, Marcucci C (Apr 2008). "Green plasma-revisited". Anesthesiology. 108 (4): 764–5. doi:10.1097/ALN.0b013e3181672668. PMID 18362615.
  13. 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". Angiology. 60 (1): 50–9. doi:10.1177/0003319708314249. PMID 18388036.
  14. Lutsenko S, Gupta A, Burkhead JL, Zuzel V (Aug 2008). "Cellular multitasking: the dual role of human Cu-ATPases in cofactor delivery and intracellular copper balance". Archives of Biochemistry and Biophysics. 476 (1): 22–32. doi:10.1016/j.abb.2008.05.005. PMC 2556376. PMID 18534184.
  15. Wolf TL, Kotun J, Meador-Woodruff JH (Sep 2006). "Plasma copper, iron, ceruloplasmin and ferroxidase activity in schizophrenia". Schizophrenia Research. 86 (1–3): 167–71. doi:10.1016/j.schres.2006.05.027. PMID 16842975.
  16. 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". Behavioral and Brain Functions. 4: 52. doi:10.1186/1744-9081-4-52. PMC 2596773. PMID 19017404.

Further reading

External links