Ceruloplasmin
Encyclopedia
Ceruloplasmin 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.
synthesized in the liver containing 6 atoms of copper
in its structure. Ceruloplasmin carries about 70% of the total copper in human plasma while albumin carries about 15%. The rest is accounted for by macroglobulins. 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 carry iron only in the ferric state. The molecular weight of human ceruloplasmin is reported to be 151kDa.
Mechanisms of low ceruplasmin 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 can lead to the rare genetic human disease aceruloplasminemia, characterized by iron overload in the brain, liver, pancreas, and retina.
called the GAIT element
is involved in the selective translational silencing of the Ceruloplasmin transcript.
The silencing requires binding of a cytosolic inhibitor complex called IFN-gamma-activated inhibitor of translation (GAIT) to the GAIT element.
Ferroxidase
Ferroxidase also known as Fe:oxygen oxidoreductase is an enzyme that catalyzes the oxidization of iron II to iron III:- Examples :Human genes encoding proteins with ferroxidase activity include:* CP – Ceruloplasmin* FTH1 – Ferritin heavy chain...
enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the CP gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Ceruloplasmin is the major copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948. Another protein, hephaestin
Hephaestin
Hephaestin also known as HEPH is a protein which in humans is encoded by the HEPH gene.-Function:Hephaestin is involved in the metabolism and homeostasis of iron and possibly copper. It is a transmembrane copper-dependent ferroxidase responsible for transporting dietary iron from intestinal...
, is noted for its homology to ceruloplasmin, and also participates in iron and probably copper metabolism.
Function
It is an enzymeEnzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
synthesized in the liver containing 6 atoms of copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
in its structure. Ceruloplasmin carries about 70% of the total copper in human plasma while albumin carries about 15%. The rest is accounted for by macroglobulins. 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
Transferrin
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...
, which can carry iron only in the ferric state. The molecular weight of human ceruloplasmin is reported to be 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 (aceruloplasminemiaAceruloplasminemiaAceruloplasminemia is an autosomal recessive disorder of iron metabolism characterized by progressive neurodegeneration of the retina and basal ganglia and diabetes mellitus....
) - Copper levels are low in general
- MalnutritionMalnutritionMalnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
/trace metal deficiency in the food source
- Malnutrition
- Copper does not cross the intestinal barrier due to ATP7AATP7ACopper-transporting ATPase 1 also known as copper pump 1 or Menkes disease-associated protein is a protein that in humans is encoded by the ATP7A gene.- Gene :...
deficiency (Menkes diseaseMenkes diseaseMenkes disease , also called Menkes syndrome, copper transport disease, steely hair disease, kinky hair disease, or Menkes kinky hair syndrome, is a disorder that affects copper levels in the body, leading to copper deficiency...
) - Delivery of copper into the lumen of the EREndoplasmic reticulumThe endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
-GolgiGolgi apparatusThe Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
network is absent in hepatocyteHepatocyteA hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...
s due to absent ATP7B (Wilson's diseaseWilson's diseaseWilson's disease or hepatolenticular degeneration is an autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver 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
Hepatocyte
A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...
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.
Decreased levels
Lower-than-normal ceruloplasmin levels may indicate:- Wilson disease (a rare copper storage disease)
- Menkes diseaseMenkes diseaseMenkes disease , also called Menkes syndrome, copper transport disease, steely hair disease, kinky hair disease, or Menkes kinky hair syndrome, is a disorder that affects copper levels in the body, leading to copper deficiency...
(Menke kinky hair syndrome) (very rare) - Overdose of Vitamin CVitamin CVitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
- CopperCopperCopper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
deficiency - AceruloplasminemiaAceruloplasminemiaAceruloplasminemia is an autosomal recessive disorder of iron metabolism characterized by progressive neurodegeneration of the retina and basal ganglia and diabetes mellitus....
Elevated levels
Greater-than-normal ceruloplasmin levels may indicate or be noticed in:- pregnancyPregnancyPregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
- oral contraceptive pill use
- lymphomaLymphomaLymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
- acute and chronic inflammationInflammationInflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
(it is an acute-phase reactant) - rheumatoid arthritisRheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
- Angina
- Alzheimer's diseaseAlzheimer's diseaseAlzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
- SchizophreniaSchizophreniaSchizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
- Obsessive-compulsive disorderObsessive-compulsive disorderObsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions...
Reference ranges
Regulation
A cis-regulatory elementCis-regulatory element
A cis-regulatory element or cis-element is a region of DNA or RNA that regulates the expression of genes located on that same molecule of DNA . This term is constructed from the Latin word cis, which means "on the same side as". These cis-regulatory elements are often binding sites for one or...
called the GAIT element
GAIT element
The gamma interferon inhibitor of translation element or GAIT element is a cis-acting RNA element located in the 3'-UTR of the ceruloplasmin mRNA....
is involved in the selective translational silencing of the Ceruloplasmin transcript.
The silencing requires binding of a cytosolic inhibitor complex called IFN-gamma-activated inhibitor of translation (GAIT) to the GAIT element.