Alpha2-glycoprotein ceruloplasmin, also known as ferroxidase or iron(II):oxygen oxidoreductase, is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It is an enzyme which catalyzes the oxidation of ferrous iron to ferric iron. The molecular weight of human ceruloplasmin is reported to be 151kDa.
Structure of CP
Protein Aminoacids Percentage
Synthesis and Turnover
The gene encoding ceruloplasmin is on chromosome 3q, located in bands 3q23-q25.
It is mainly synthesized in the liver by hepatocytes and reticuloendothelial cells and it doesn’t cross the hematoencephalic barrier. It is secreted into plasma as oloceruloplasmin containing 6 atoms of copper in its structure.
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.
Ceruloplasmin is characterized from the structural point of view by presenting three types of binding sites for copper, and from the functional point of view, to catalyze the reduction of an oxygen molecule with formation of water, without releasing intermediaries potentially toxic (O2-, H2O2
). Ceruloplasmin carries 95% of the copper in our plasma. CP has an oxidase activity nonspecific and is involved in oxidation reactions of various organic and inorganic substrates in vitro, eg Fe2+, benzidine, p-phenylenediamine, and others. Only the Fe2+ ion is considered a biological substrate for this enzyme. Catalyzes the conversion of iron from ferrous
(Fe2+) to ferric
form (Fe3+), therefore assisting in its transport in the plasma in association with transferrin
, which can only carry iron in the ferric state. The copper in ceruloplasmin plays an important role in the oxidation of iron before it is transported to the plasma.
The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum. Osaki S, Johnson DA, Frieden E. J Biol Chem. 1966 Jun 25;241(12):2746-51
Ceruloplasmin is essential for the proper localization of ferroportin
(MTP1),%20Ferroportin on the plasma membrane in different cell types, like astrocytes or macrophages.
In the brain, the majority of CP is localized in astrocytes in the nervous system and in the nuclei and ganglion cells that relate to the retina.
Glycosilphosphatidylinositol-anchored ceruloplasmin is required for iron efflux from cells in the central nervous system. Jeong SY, David S. J. Biol. Chem. 2003:278:27144-48
Levels drop in patients with hepatic disease due to reduced synthesizing capabilities.
In hereditary diseases of copper metabolism dependent, as in Wilson's disease
and syndrome of Melk, the concentration of ceruloplasmin is greatly diminished. This becomes even more evident in homozygous carriers of these diseases. Lowering levels of ceruloplamin is also found in cases of liver failure and loss of protein. Moreover, ceruloplasmin is reduced in the case of hereditary hemochromatosis
due to a mutation of the HFE
In the presence of inflammation, cholestasis, and oral contraceptives is determined increased serum concentration of ceruloplasmin. Interferon γ induces the synthesis of mRNA and protein, but after about 16 hours the translation is inhibited.
Mutations in the ceruloplasmin gene can lead to the rare genetic human disease aceruloplasminemia, characterized by iron overload in the brain, liver, pancreas, and retina. Numerous mutations have been identified.
Some authors find that cell iron overload induced a significant decrease in CP protein content in the cells and that treatment with iron chelators led to a significant increase in CP protein level in the cells.
Ceruloplasmin expression and its role in iron transport in C6 cells. Chang, Y.Z., Qian, Z.M., Du, J.R., Zhu, L., Xu, Y., Li, L.Z., Wang, C.Y., Wang, Q., Ge, X.H., Ho, K.P., Niu, L., Ke, Y. Neurochem. Int.
It is determined in the serum to confirm the diagnosis of Aceruloplasminemia.