The role of ceruloplasmin in iron metabolism.
Open accessAbstract
The importance of ceruloplasmin in iron metabolism was studied in swine made hypoceruloplasminemic by copper deprivation. When the plasma ceruloplasmin level fell below 1% of normal, cell-to-plasma iron flow became sufficiently impaired to cause hypoferremia, even though total body iron stores were normal. When ceruloplasmin was administered to such animals, plasma iron increased immediately and continued to rise at a rate proportional to the logarithm of the ceruloplasmin dose. The administration of inorganic copper induced increases in plasma iron only after ceruloplasmin appeared in the circulation. Thus, ceruloplasmin appeared to be essential to the normal movement of iron from cells to plasma. Studies designed to define the mechanism of action of ceruloplasmin were based on the in vitro observation that ceruloplasmin behaves as an enzyme (ferroxidase) that catalyzes oxidation of ferrous iron. Retention of injected ferrous iron in the plasma of ceruloplasmin-deficient swine was significantly less than that of ferric iron, reflecting impaired transferrin iron binding. Rat ceruloplasmin, which has little ferroxidase activity, was much less effective than porcine or human ceruloplasmin in inducing increases in plasma iron. These observations suggest that ceruloplasmin acts by virtue of its ferroxidase activity. Eight patients with Wilson's disease were evaluated in order to investigate iron metabolism in a disorder characterized by reduced ceruloplasmin levels. Evidence of iron deficiency was found in six of these, and in five of the six, plasma ceruloplasmin was less than 5% of normal. In comparison, the two patients without evidence of iron deficiency had ceruloplasmin levels of 11 and 18% of normal. It is suggested that iron deficiency tends to occur in those patients with Wilson's disease who have the severest degrees of hypoceruloplasminemia, possibly because of defective transfer of iron from intestinal mucosal cells to plasma.
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Transport by ferroportin is facilitated by multicopper ferroxidases including ceruloplasmin and its membrane-bound intestinal homolog hephaestin.
“Transport is facilitated by multicopper ferroxidases including the abundant serum protein ceruloplasmin and its membrane-bound intestinal homolog hephaestin.”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [82]
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Does Ceruloplasmin Defend Against Neurodegenerative Diseases?
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Pathogenesis of Wilson disease
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A prospective study of serum copper and zinc levels in patients receiving total parenteral nutrition
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Inhibition by superoxide dismutase of methemoglobin formation from oxyhemoglobin.
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Iron Storage Disorders of the Liver
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Copper in Human Health and Disease: A Comprehensive Review
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“Ceruloplasmin also has a role in the creation of energy, synthesis of neurotransmitters, formation of connective tissue and distribution of copper to different tissues and organs where it facilitates the action of copper ‐ dependent enzymes [37 – 40].”
Copper imbalance in Alzheimer’s disease: Convergence of the chemistry and the clinic
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Caeruloplasmin: A Plasma Protein, Enzyme, and Antioxidant
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“It has been estimated that no more than 5–10% of the CP in plasma is sufficient to perform all its iron-related functions (Roeser et al. 1970; Osaki et al. 1971), so is the excess simply ‘reserve’ iron oxidizing capacity, or does the protein perform other functions? Furthermore, HEPH is expressed at high levels throug…”
BackgroundFerreira, C. R., & Gahl, W. A. (2017) · Translational Science of Rare Diseases · doi:10.3233/trd-170015 · Cited by 75 · see citing works
“Specifically, the ferroxidase activity of ceruloplasmin is required to oxidize ferrous to ferric iron for incorporation into transferrin and subsequent transport out of cells [179].”
BackgroundGenetic Disorders Affecting Proteins of Iron Metabolism: Clinical Implications
Sheth, S., & Brittenham, G. M. (2000) · Annual Review of Medicine · doi:10.1146/annurev.med.51.1.443 · Cited by 74 · see citing works
The copper-iron connection: Hereditary aceruloplasminemia
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Increased plasma lipid peroxidation in patients with aceruloplasminemia
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Molecular mechanisms of copper homeostasis
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Serum oxidant/antioxidant status in patients with Behçet's disease.
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Dependence of intestinal iron absorption on the valency state of iron
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“Since species differences seemed to be irrelevant in this context, commercially available human ceruloplasmin was used for the further investigations, the ferro-oxidase activity of which is higher than that of rat ceruloplasmin (Roeser et al. 1970).”
BackgroundEffect of Copper Deficiency on Erythrocyte Membrane Proteins of Rats
Johnson, W. T., & Kramer, T. R. (1987) · Journal of Nutrition · doi:10.1093/jn/117.6.1085 · Cited by 68 · see citing works
The Role of Hepcidin in Iron Homeostasis and Anemia in Hemodialysis Patients
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Caeruloplasmin: A Multi‐Functional Metalloprotein of Vertebrate Plasma
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Free copper in serum: An analytical challenge and its possible applications
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Biochemical markers for the diagnosis and monitoring of Wilson Disease
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Hepatic iron accumulation in copper-deficient rats
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“Such an increase was not observed by Weisenberg et al. (1980), but similar elevations have been seen in Cu-deficient rats (Evans & Abraham, 1973; Owen, 1973) and swine (Lee et al. 1968, 1976; Roeser et al. 1970) receiving Fe orally or parenterally.”
BackgroundResultCabrera, A., Alonzo, E., Sauble, E., Chu, Y.-L., Nguyen, D., Linder, M. C., Sato, D. S., & Mason, A. Z. (2008) · BioMetals · doi:10.1007/s10534-008-9139-6 · Cited by 65 · see citing works
“…of ceruloplasmin-deficient dogs (Osaki and Johnson 1969) or pigs (Ragan et al. 1969) results in the immediate release of iron into the blood, although it appears that only extremely low levels of active ceruloplasmin (\1% of normal) reduce iron transport and accumulation (Roeser et al. 1980).”
BackgroundCOMPARATIVE NUTRITIONOF IRON AND COPPER
Winzerling, J. J., & Law, A. J. H. (1997) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.17.1.501 · Cited by 65 · see citing works
The formation of Fe3+-transferrin-CO3(2-) via the binding and oxidation of Fe2+.
Kojima, N., & Bates, G. W. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43229-2 · Cited by 65 · see citing works
- Authors
- Roeser, H. P., Lee, G. R., Nacht, S., & Cartwright, G. E.
- Affiliations
- University of Utah (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1970-12-01
- Volume
- 49
- Issue
- 12
- Pages
- 2408-2417
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC322742
- OpenAlex
- W1993916376
- Cited by
- 365
- References
- 22
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 8 · 2023: 4 · 2022: 8 · 2021: 10 · 2020: 5 · 2019: 10 · 2018: 8 · 2017: 11 · 2016: 6 · 2015: 3 · 2014: 7 · 2013: 2 · 2012: 3
- FWCI
- 6.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Royal Australasian College of Physicians
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- ceruloplasmin, iron metabolism, ferroxidase activity, hypoferremia, transferrin iron binding, iron deficiency, Wilson's disease, plasma iron, porcine model
- MeSH terms
- Animals, Ceruloplasmin, Copper, Deficiency Diseases, Hepatolenticular Degeneration, Humans, Injections, Intravenous, Iron, Protein Binding, Swine, Rats
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