Ceruloplasmin

Ceruloplasmin Keeps Your Copper Safe

Ceruloplasmin is a copper-containing protein produced primarily by the liver, though some is produced in lymphocytes and macrophages.[1]

It binds and carries up to 95% of circulating copper and is considered the most sensitive marker of copper deficiency.[2] <[3] Ceruloplasmin also has important antioxidant properties as an oxidase enzyme in iron, copper, and glutathione metabolism.[4] It possess nitric oxidase (NO) catalytic activity and helps regulate NO homeostasis.[5]

Measuring serum ceruloplasmin assists in diagnosing Wilson’s disease, Menkes disease, abnormal copper metabolism, and copper deficiency.

Menkes disease is a genetic disorder characterized by decreased ceruloplasmin and inability to remove copper, allowing abnormal levels of intracellular copper to build up.[6] Wilson’s disease is an inherited disorder of copper metabolism in which serum levels of ceruloplasmin may be low or normal despite increasing levels in the brain, liver, and other organs.[7]

Ceruloplasmin is an acute phase reactant and may be elevated in infection, cardiovascular disease, arthritis, and other inflammatory conditions. Elevated ceruloplasmin levels strongly correlate with hs-CRP and are considered an independent risk factor for cardiac events. In general, elevated ceruloplasmin tends to be more common in older females with cardiovascular risk factors such as dyslipidemia and diabetes, as well as reduced renal function.[8]

As availability of copper decreases, so does ceruloplasmin. Deficiency of copper is characterized by reduced energy production; alterations in glucose and cholesterol metabolism; accumulation of tissue iron; increased oxidative stress; altered immune cell structure and function; impairment of the electrical activity and contractility of the heart; disruption of neuropeptide synthesis and function; and aberrations in neurobehavioral stability.[9]

Ceruloplasmin plays a vital role in iron metabolism by oxidizing ferrous iron to its less toxic ferric form. It assists in the mobilization of iron from tissue stores into serum, where it can then be safely transported by transferrin.[10] Low ceruloplasmin will reduce circulating iron and hemoglobin, contributing to anemia.[11]

Lack of ceruloplasmin, as occurs in the genetic disorder aceruloplasminemia, can cause a toxic buildup of iron in sensitive tissues, such as the pancreas, resulting in diabetes in these genetically predisposed individuals.[12]

Ceruloplasmin has an extensive range of clinical utility and provides another tool in the optimal diagnosis toolbox. For more comprehensive assessment, serum and RBC copper should be evaluated along with ceruloplasmin. Further evaluation of inflammation, including hs-CRP, ferritin, homocysteine, fibrinogen, IL-6, and neutrophil-to-lymphocyte ratio, would be prudent as well.

References

1. Lopez MJ, Royer A, Shah NJ. Biochemistry, Ceruloplasmin. 2020 Feb 5.  

2. Healy J, Tipton K. Ceruloplasmin and what it might do. J Neural Transm (Vienna). 2007;114(6):777-81. 

3. National Research Council (US) Committee on Copper in Drinking Water. Copper in Drinking Water. Washington (DC): National Academies Press (US); 2000. 3, Health Effects of Copper Deficiencies. 

4. Healy J, Tipton K. Ceruloplasmin and what it might do. J Neural Transm (Vienna). 2007;114(6):777-81. Epub 2007 Apr 4. Review. PubMed PMID: 17406962. 

5. Tang WH, Wu Y, Hartiala J, et al. Clinical and genetic association of serum ceruloplasmin with cardiovascular risk. Arterioscler Thromb Vasc Biol. 2012 Feb;32(2):516-22.  

6. Tümer Z, Møller LB. Menkes disease. Eur J Hum Genet. 2010 May;18(5):511-8. [R]

7. Yüce A, Koçak N, Ozen H, Gürakan F. Wilson's disease patients with normal ceruloplasmin levels. Turk J Pediatr. 1999 Jan-Mar;41(1):99-102. 

8. Tang WH, Wu Y, Hartiala J, et al. Clinical and genetic association of serum ceruloplasmin with cardiovascular risk. Arterioscler Thromb Vasc Biol. 2012 Feb;32(2):516-22.  

9. Hordyjewska A, Popiołek Ł, Kocot J. The many "faces" of copper in medicine and treatment. Biometals. 2014 Aug;27(4):611-21.  

10. Diouf I, Bush AI, Ayton S; Alzheimer's disease Neuroimaging Initiative. Cerebrospinal fluid ceruloplasmin levels predict cognitive decline and brain atrophy in people with underlying β-amyloid pathology. Neurobiol Dis. 2020 Jun;139:104810 

11. Mahan, L. K., & Raymond, J. L. (2016). Krause's Food & the Nutrition Care Process, Mea Edition E-Book. Elsevier.

12. National Research Council (US) Committee on Copper in Drinking Water. Copper in Drinking Water. Washington (DC): National Academies Press (US); 2000. 3, Health Effects of Copper Deficiencies. 

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