Ceruloplasmin is a copper- containing protein ( glycoprotein ) present in blood plasma . Ceruloplasmin contains about 95% of the total amount of copper in human serum [1] . Congenital deficiency of ceruloplasmin leads to defects in the development of the brain and liver . It was described in 1948 [2] .
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| Symbol | CP-2 | ||||||||||||
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| Ceruloplasmin (ferroxidase) | |
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| Designations | |
| Characters | CP CP-2 |
| Entrez gene | 1356 |
| Hgnc | 2295 |
| Omim | 117700 |
| Refseq | NM_000096 |
| Uniprot | P00450 |
| Other data | |
| Cipher cf | 1.16.3.1 |
| Locus | 3rd hr. , 3q23-q24 |
Content
- 1 Physical properties of human ceruloplasmin
- 2 Physiological role
- 3 Clinical significance
- 4 Animal studies
- 5 See also
- 6 notes
- 7 References
Physical properties of human ceruloplasmin
Human ceruloplasmin, due to its copper ions, has a blue color. The average molecular weight ranges from 150,000 to 160,000 g / mol [3] . There are 6-7 copper ions (Cu +2 ) per molecule.
Before the introduction of copper into protein, it is called apo ceruloplasmin, after - holo ceruloplasmin.
It has been shown that the human ceruloplasmin gene undergoes alternative splicing . [four]
The main amino acids of ceruloplasmin: aspartic , glutamine , threonine , glycine , leucine .
Physiological Role
Ceruloplasmin is found not only in the plasma of humans and primates, but also in pigs, horses, goats, deer, dogs, cats and other animals. Protein plays an important enzymatic role - it catalyzes the oxidation of polyphenols and polyamines in plasma [3] .
The synthesis of ceruloplasmin in the liver is carried out by hepatocytes and the rate of this process is regulated by hormones. Throughout life, the level of this protein in plasma remains stable, with the exception of the neonatal stage and the period of pregnancy in women.
Ceruloplasmin does not penetrate or weakly penetrates the blood-brain barrier . In the human brain , protein is produced by certain populations of glial cells associated with microvessels, and in the retina by the cells of the inner nuclear layer. [5] Astrocytes synthesize a special form of ceruloplasmin, [6] generated by alternative splicing and containing a GPI anchor, it is supposedly necessary for removing iron from the central nervous system cells. [7]
Clinical Importance
Decreased levels of ceruloplasmin are noted in Wilson-Konovalov disease and Menkes disease . In the first case, this is due to a violation of the process of “loading” apoceruloplasmin with copper due to mutations in the ATP7B gene. In the second case, impaired copper uptake in the intestine due to mutations in the ATP7A gene.
The concentration of ceruloplasmin also increases with inflammatory processes, injuries.
A number of studies have reported elevated levels of ceruloplasmin in patients with schizophrenia . [8] Elevated levels of ceruloplasmin were also noted in the currently only small study of individuals with obsessive-compulsive disorder . [9]
Animal Research
In ceruloplasmin knockout mice, iron deposition in the cerebellum and brain stem, loss of dopaminergic neurons, and impaired motor coordination are noted. [10]
See also
- ATP7B - introduces copper into ceruloplasmin
- ATP7A
- Hephaestin ( HEPH gene) - Ceruloplasmin homolog
Notes
- ↑ Analysis for ceruloplasmin
- ↑ Holmberg CG, Laurell CB. Investigations in serum copper. II. Isolation of the Copper containing protein, and a description of its properties (English) // Acta Chem Scand : journal. - 1948. - Vol. 2 . - P. 550-56 . - DOI : 10.3891 / acta.chem.scand.02-05-05 .
- ↑ 1 2 Inorganic Biochemistry / Edited by G. Eichhorn, trans. from English., Volume 1, M .: Mir, 1978
- ↑ Alternative RNA splicing generates a glycosylphosphatidylinositol-anchored form of ceruloplasmin in mammalian brain. Patel BN, Dunn RJ, David S. J Biol Chem. 2000 Feb 11; 275 (6): 4305-10. PMID 10660599
- ↑ Klomp, LWJ; Gitlin, JD: Expression of the ceruloplasmin gene in the human retina and brain: implications for a pathogenic model in aceruloplasminemia. Hum. Molec. Genet. 5: 1989-1996, 1996. PMID 8968753
- ↑ A novel glycosylphosphatidylinositol-anchored form of ceruloplasmin is expressed by mammalian astrocytes. Patel BN, David S. J Biol Chem. 1997 Aug 8; 272 (32): 20185-90. PMID 9242695
- ↑ Glycosylphosphatidylinositol-anchored ceruloplasmin is required for iron efflux from cells in the central nervous system. Jeong SY, David S. J Biol Chem. 2003 Jul 18; 278 (29): 27144-8. Epub 2003 May 12. PMID 12743117
- ↑ Plasma copper, iron, ceruloplasmin and ferroxidase activity in schizophrenia. Wolf TL, Kotun J, Meador-Woodruff JH. Schizophr Res. 2006 Sep; 86 (1-3): 167-71. Epub 2006 Jul 13. PMID 16842975
- ↑ High ceruloplasmin levels are associated with obsessive compulsive disorder: a case control study. Virit O, Selek S, Bulut M, Savas HA, Celik H, Erel O, Herken H. Behav Brain Funct. 2008 Nov 18; 4: 52. PMID 19017404
- ↑ Ceruloplasmin regulates iron levels in the CNS and prevents free radical injury. Patel BN, Dunn RJ, Jeong SY, Zhu Q, Julien JP, David S. J Neurosci. 2002 Aug; 22 (15): 6578-86. PMID 1215153
Links
- Ceruloplasmin - Institute of Experimental Medicine, St. Petersburg
- Ceruloplasmin - from metabolite to drug - V. I. Vashchenko, T. N. Vashchenko, 2006, “Psychopharmacology and Biological Addiction”