Ceruloplasmin (or caeruloplasmin) is officially known as ferroxidase or iron(II):oxygen oxidoreductase. It is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948.

Function

It is an enzyme synthesized in the liver containing 6 atoms of copper in its structure. Ceruloplasmin carries 90% of the copper in our plasma. The other 10% is carried by albumin, albumin may be confused at times to have a greater importance as a copper carrier because it binds copper less tightly than ceruloplasmin. 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 only carry iron in the ferric state. The molecular weight of human ceruloplasmin is reported as 151kDa.

Pathology

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

• Mechanisms of low ceruplasmin levels:
• Gene expression genetically low: aceruloplasminemia
• Copper levels are low in general:
• Malnutrition/trace metal deficiency in the food source
• Copper does not cross the intestinal barrier due to ATP7A deficiency in Menkes disease
• Delivery of copper into the lumen of the ER-Golgi network is absent in hepatocyte due to absent ATP7B in Wilson's disease.

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 can lead to the rare genetic human disease aceruloplasminemia, characterized by iron overload in the brain, liver, pancreas, and retina.

Interpretation

Decreased levels

Lower-than-normal ceruloplasmin levels may indicate:

• Menkes disease (Menke's kinky hair syndrome) (very rare)
• Wilson's disease (a rare copper storage disease)
• Overdose of vitamin C
• Copper deficiency
• Aceruloplasminemia

Elevated levels

Greater-than-normal ceruloplasmin levels may indicate:

• pregnancy
• lymphoma
• acute and chronic inflammation (it is an acute-phase reactant)
• rheumatoid arthritis

References

Further reading