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The role of ceruloplasmin in iron metabolism.
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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 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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Olivares, M., Araya, M., Pizarro, F., & Letelier, A. (2006) · Biological Trace Element Research · doi:10.1385/bter:112:3:213 · Cited by 6
“Ceruloplasmin, the major copper-binding protein in serum, is crucial to transform Fe2+ to Fe3+ because of its ferroxidase action, a step indispensable for the incorporation of iron into circulating transferrin (2).”
BackgroundCopper-Induced Epigenetic Changes Shape the Clinical Phenotype in Wilson’s Disease
Fanni, D., Gerosa, C., Nurchi, V. M., Cappai, R., Mureddu, M., Eyken, P. V., Saba, L., Manchia, M., & Faa, G. (2020) · Current Medicinal Chemistry · doi:10.2174/0929867327666200730214757 · Cited by 6
Poujois, A., & Woimant, F. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-811077-5.00010-4 · Cited by 6
Osmotically induced changes in copper and iron concentrations in three euryhaline crustacean species
Spaargaren, D. H. (1983) · Netherlands Journal of Sea Research · doi:10.1016/0077-7579(83)90008-x · Cited by 6
Influence of Dietary Lipids on Iron and Copper Levels of Rats Administered Oral Contraceptives
Onderka, H. K., & Kirksey, A. (1975) · Journal of Nutrition · doi:10.1093/jn/105.10.1269 · Cited by 6
Kim, J. J., Grassmann, E., & Kirchgeßner, M. (1981) · Zentralblatt für Veterinärmedizin Reihe A · doi:10.1111/j.1439-0442.1981.tb01221.x · Cited by 6
Hereditary deficiency of ferroxidase (aka caeruloplasmin)
Logan, J. I. (1996) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.61.5.431 · Cited by 6
Azevedo-Repossi, R. D. F., Brito, R., Cossenza, M., dos Santos‐Rodrigues, A., Ferreira, G. C., Petrs‐Silva, H., Calaza, K. D. C., & Madeira, L. F. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05197-6 · Cited by 6
“Ceruloplasmin, a copper-binding protein, also exhibits this ferroxidase activity and contributes to iron homeostasis, thereby supporting iron sequestration and reducing oxidative stress [33].”
The Role of Copper in Metabolic Disorders
Evans, G. W. (1981) · Springer eBooks · doi:10.1007/978-1-4615-9200-6_7 · Cited by 5
Serum iron in acute myocardial infarction
Handjani, A. M., Banihashemi, A., Rafiee, R., & Tolou, H. (1971) · Annals of Hematology · doi:10.1007/bf01632799 · Cited by 5
The molecular mechanisms of cuproptosis and its role in central nervous system diseases
Xu, M., An, Y., Liu, X., Li, X., Huang, X., Gu, Q., Xue, M., Xue, J., Tao, L., Shan, H., et al. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.112236 · Cited by 5
Budzyń, M., Iskra, M., Wielkoszyński, T., Małecka, M., & Gryszczyńska, B. (2012) · Journal of Elementology · doi:10.5601/jelem.2009.14.2.02 · Cited by 4
“The level of reactive iron in human organism is precisely regulated by ceruloplasmin (ROESER et al. 1970, STOCKS et al. 1974) blue plasma copper protein, composed of three 42-45 kDa domains that are homologous to each other (ORTEL et al. 1984) and similar to domains in factors V and VIII of…”
BackgroundThe effect of potassium and magnesium infusion on plasma Mg concentration and Mg balance in ewes
McLean, A. F., Buchan, W., & Scott, D. (1985) · British Journal Of Nutrition · doi:10.1079/bjn19850157 · Cited by 4
Astrocytes in Aceruloplasminemia
Miyajima, H. (2018) · InTech eBooks · doi:10.5772/intechopen.71831 · Cited by 5
Matusiak, K., Dróźdż, A., Setkowicz, Z., Kubala‐Kukuś, A., Stabrawa, I., Ciarach, M., Janeczko, K. J., Horák, D., Babič, M., & Chwiej, J. G. (2020) · Metallomics · doi:10.1039/d0mt00158a · Cited by 4
Complementary and Alternative Medicine
Price, K. N., Thompson, A. M., & Shi, V. Y. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-77724-7.00028-0 · Cited by 4
Yoshida, K. (1999) · Springer eBooks · doi:10.1007/978-1-4615-4723-5_23 · Cited by 4
Genetic Susceptibility to Heavy Metals in the Environment
Cox, D. W., Cullen, L. M., & Forbes, J. (2002) · CRC Press eBooks · doi:10.1201/9780203909300.ch16 · Cited by 3
Iron deficiency anemia in suckling piglets: When physiology cannot keep up with breeding goals
Lipiński, P., Starzyński, R. R., Lenartowicz, M., Wang, X., Ogłuszka, M., & Batorska, M. (2025) · The Veterinary Journal · doi:10.1016/j.tvjl.2025.106530 · Cited by 4
Metadata
- 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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