Ceruloplasmin (CP)

Ceruloplasmin (or caeruloplasmin) is a ferroxidase enzyme that in humans is encoded by the CP gene.

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. Another protein, hephaestin, is noted for its homology to ceruloplasmin, and also participates in iron and probably copper metabolism.

This test is used to measure how much of a copper-containing protein is in blood. This test is used to diagnose problems related to copper, such as Wilson disease. Wilson disease is a rare inherited disease. It causes too much copper in blood.

Ceruloplasmin is a protein made in the liver. It stores and carries the mineral copper around the body. Ceruloplasmin carries 65% to 90% of the copper found in blood. Copper is vital to many processes in body. These include building strong bones and making melanin. But having too much copper in body can be toxic.

The liver normally takes copper from the bloodstream and puts it into ceruloplasmin proteins. The ceruloplasmin is then released into blood plasma. Ceruloplasmin carries copper around the body to the tissues that need it.

In Wilson's disease, copper is not put in ceruloplasmin. The disease also keeps the liver from sending extra copper to be eliminated in bowel movements. Instead, copper builds up in the liver until it overflows into the bloodstream. From there, copper builds up in the brain, corneas, kidneys, liver, bones, and small glands near the thyroid. If not treated, the liver and brain damage due to copper poisoning from Wilson disease is fatal.

Ceruloplasmin is an enzyme, synthesized in the liver containing 6 atoms of copper in its structure. Ceruloplasmin carries more than 95% of the total copper in healthy human plasma. 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.

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 (Menkes disease)

- Delivery of copper into the lumen of the ER-Golgi network is absent in hepatocytes due to absent ATP7B (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 (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.

Deficiency

Lower-than-normal ceruloplasmin levels may indicate the following:

Wilson disease (a rare (UK incidence 1/100,000) copper storage disease)

Menkes disease (Menkes kinky hair syndrome) (rare - UK incidence 1/100,000)

Overdose of Vitamin C

Copper deficiency

Aceruloplasminemia

Excess

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

pregnancy

oral contraceptive pill use

Cancer (breast or lymphoma)

acute and chronic inflammation (it is an acute-phase reactant)

rheumatoid arthritis

Angina

Alzheimer's disease

Schizophrenia

Obsessive-compulsive disorder

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