Cited by 365Iron Metabolism and DisordersTrace Elements in HealthNeurological diseases and metabolism

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The role of ceruloplasmin in iron metabolism.

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Roeser, H. P., Lee, G. R., Nacht, S., Cartwright, G. E.·1970·Journal of Clinical Investigation

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Abstract

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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The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum.
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H. P. Roeser, G. R. Lee, S. Nacht, and G. E. Cartwright 7. Nacht, S., G. R. Lee, and G. E. Cartwright. 1968. Large scale preparation of porcine ceruloplasmin. Fed. Proc. 27: 482. (Abstr.)
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Authors: Roeser, H. P., Lee, G. R., Nacht, S., & Cartwright, G. E.
Affiliations: University of Utah (US)
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1970-12-01
Volume: 49
Issue: 12
Pages: 2408-2417
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci106460
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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The role of ceruloplasmin in iron metabolism.

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