Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 34 year old diabetic man with a complete deficiency of serum ferroxidase activity, regardless of the presence of serum ceruloplasmin (Cp), a multicopper ferroxidase protein, is described. The patient had had diabetes mellitus for 13 years, and was also found to have retinal degeneration accompanied by the development of a hearing disturbance of unknown aetiology. Laboratory examination showed markedly increased serum ferritin and low serum iron. Magnetic resonance imaging showed a pronounced hypointensity in the putamen, caudate, cerebellar dentate, and thalamus on T2 weighted images, and also disclosed a low level signal in the liver, suggesting the accumulation of some magnetic substances in the brain and liver. Liver biopsies histochemically identified iron deposition in the hepatocytes. Most of these findings were consistent with the newly established autosomal recessive disease "aceruloplasminaemia", except for the presence of serum Cp and the lack of apparent neurological symptoms. Interestingly, no ferroxidase activity was detected in the patient's serum, whereas suppressed ferroxidase activity was found in his mother's serum. A nucleotide sequence analysis of the Cp gene showed two mutations; a C to T substitution at nucleotide 2701 in exon 16, resulting in a nonsense mutation at amino acid 882 (Arg882ter), and a T to G substitution at nucleotide 2991 in exon 17, resulting in an amino acid alternation at amino acid 978 (His978Gln). The second mutation was also found in the patient's mother. The absence of serum ferroxidase activity despite the presence of serum Cp protein in this compound heterozygote was considered to be due to the production of a non-functional Cp harbouring no ferroxidase activity.
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PMID:A case of aceruloplasminaemia: abnormal serum ceruloplasmin protein without ferroxidase activity. 1190 23

The intimate relationship between Fe and Cu in human nutrition has been recognised for many years. The best-characterised link is provided by caeruloplasmin, a multiCu-binding protein that acts as a serum ferrioxidase and is essential for the mobilisation of Fe from storage tissues. Decreased Cu status has been shown to reduce holo-caeruloplasmin production and impair ferrioxidase activity, leading, in a number of cases, to decreased tissue Fe release and the generation of anaemia that is responsive to dietary supplementation with Cu but not Fe. Dietary Fe absorption also requires the presence of a multiCu ferrioxidase. Hephaestin, a caeruloplasmin homologue, works in concert with the IREG1 transporter to permit Fe efflux from enterocytes for loading onto transferrin. The essential role of hephaestin in this process has been recognised from studies in the sex-linked anaemic (sla) mouse, in which Fe efflux is markedly impaired as a result of a mutation in the hephaestin gene that results in a truncated and non-functional version of the protein. There is emerging evidence that a number of other components of the intestinal Fe transport pathway are also Cu sensitive. Divalent metal transporter 1 (DMT1), the Fe transporter located at the apical membrane of enterocytes, is also a physiologically-relevant Cu transporter, suggesting that these two metals may compete with each other for uptake into the duodenal enterocytes. Furthermore, expression of both DMT1 and the basolateral Fe-efflux transporter IREG1 can be regulated by Cu, suggesting that the Fe-Cu relationship may be more complex than first thought.
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PMID:The molecular basis of copper and iron interactions. 1583 Nov 28