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)

The isolated human trophoblast was used as a system to analyze the effects of different physiological ligands on cellular uptake of copper. The results show that the uptake of copper by these cells follows a similar pattern for the ligands tested (histidine, albumin and ceruloplasmin) as that for copper chloride. The process follows a typical hyperbolic curve at 37 degrees C. The initial phase of uptake follows a linear pattern during 30 min at 37 degrees C and at least 60 min at 4 degrees C from which the uptake rate is calculated. However, a significant decrease in the uptake rate is observed for albumin. The effect of histidine on stimulating copper transport is observed in the presence of serum, a phenomenon which is considered to be due to the release of copper that is bound to albumin. These results support the role of ceruloplasmin as a copper transport protein which releases copper at the cell surface, and a subsequent transport of the released copper in a manner similar to that of copper chloride or copper-histidine complexes.
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PMID:Uptake of 67Cu by isolated human trophoblast cells. 161 32

Alterations in zinc (Zn) and copper (Cu) homeostasis have been reported during the acute recovery period following thermal injury in both children and adults. Increased urinary losses of Zn and Cu and decreased plasma concentrations of Zn, Cu, and ceruloplasmin (CP), the major copper transport protein, occur despite adequate provision of these elements in enteral feedings. We now report data for moderately to severely burned children receiving total parenteral nutrition (TPN) supplemented to provide Zn and Cu. Hyperzincuria occurred consistently when 50 micrograms/kg Zn was delivered daily to older children. Similarly, when younger children received 100 micrograms/kg Zn daily, profound hyperzincuria ensued despite a reduction in total plasma Zn. Hypozincemia was accompanied by low levels of Zn in the plasma subfraction normally associated with albumin-bound Zn. The delivery of Cu via TPN was 4-12 micrograms/kg daily, and urinary Cu losses were not elevated. Plasma total Cu and plasma CP were invariably reduced. These findings are discussed in relation to guidelines published for pediatric trace element supplementation during TPN.
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PMID:Zinc and copper status of severely burned children during TPN. 190 24

Ferroxidase activity was increased in the aqueous humor from inflamed eyes compared to their uninflamed contralateral controls 24 h after intravitreal injection of 10 ng of endotoxin. Changes in ferroxidase activity and copper concentration paralleled each other indicating that the plasma copper transport protein ceruloplasmin (plasma ferroxidase) entered the inflamed aqueous humor from plasma through disrupted blood ocular barriers. The presence of ferroxidase activity would facilitate the removal of potentially damaging, free radical generating Fe+2. Therefore, plasma proteins may perform important protective functions in the inflamed intraocular fluids.
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PMID:Ferroxidase activity increases in the aqueous humor during the ocular inflammatory response. 267 23

The copper transport protein, ceruloplasmin, is suggested to have a role in cancer since it is involved in angiogenesis and neovascularization. In order to understand the role of ceruloplasmin in malignant cells, we have recently isolated and sequenced a human ceruloplasmin cDNA clone. In the present study, we have investigated the ceruloplasmin gene expression in human colon and breast cancer cell lines. The poly (A) RNA from human colon (WiDr) and human breast (MCF-7) cancer cell lines was analyzed for the presence of ceruloplasmin mRNA. The Northern blot analysis revealed the presence of a 3.7 kb band of ceruloplasmin mRNA in these cell lines. Dot blot analysis revealed that ceruloplasmin mRNA is at least three fold more abundant in tumor cells as compared to normal rat liver.
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PMID:Ceruloplasmin gene expression in human cancer cells. 358 57

We examined the distribution of copper among four components of human serum separated by chromatography on Sephadex G-150 and Affi-gel blue. Analysis of copper by furnace atomic absorption indicated that normal adults have copper at an average of 600 ng/ml associated with ceruloplasmin; at 120 ng/ml with transcuprein, a new copper transport protein; at 150 ng/ml with albumin; and at 90 ng/ml with one to three components of low molecular weight (less than 30,000). Cancer patients had more total copper but similar proportions in the four serum fractions. In both groups, some individuals had very high levels of copper in transcuprein, albumin, and/or one or more components of the low-molecular-weight fraction. The results showed that, contrary to earlier conclusions, ceruloplasmin copper only comprised about 60% of the total in human serum; and not just ceruloplasmin but also other forms of serum copper may be elevated in cancer patients.
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PMID:Distribution of copper among components of human serum. 386 Jun 83

The relative uptake of copper from ceruloplasmin and non-ceruloplasmin plasma pools, by normal and malignant cells, was investigated in vivo and in vitro, using 64Cu and 67Cu. 1. Most of the copper administered intravenously to normal and tumor-bearing rats was removed within 1 h, a substantial portion entering the liver. There were differences in the apparent avidity of individual tissue for ceruloplasmin vs. ionic copper, but when calculated on the basis of actual microgram absorbed, all showed a preference for ceruloplasmin. 2. Appreciable amount of copper from either source were also absorbed by the tumors, and cultured Ehrlich ascites tumor cells showed a rapid uptake and marked preference for ceruloplasmin over non-ceruloplasmin copper, as did primary rat muscle cell cultures. 3. Ceruloplasmin protein was also absorbed by normal and neoplastic rat tissues, but less rapidly than ceruloplasmin copper, as determined by administration of pure [3H]leucine- or [125I]ceruloplasmin. Copper deficiency did not accelerate this process. 4. It is concluded that, at least in rat, ceruloplasmin is the preferred plasma source of copper for normal and malignant cells, and that the copper on ceruloplasmin turns over more rapidly than the protein moiety, a finding consistent with its role as a copper transport protein.
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PMID:Circulating ceruloplasmin is an important source of copper for normal and malignant animal cells. 730 77

Copper serves as the cofactor for a number of important enzymes in cartilage, as well as in other tissues, including lysyl oxidase, superoxide dismutase, and cytochrome oxidase. Ceruloplasmin is responsible for the transport of approx. 95% of the copper in serum, but the mechanisms for intracellular copper transport are unknown. We have demonstrated recently that a high-molecular-weight cartilage glycoprotein, referred to as CMGP, has regions of sequence homology with ceruloplasmin. CMGP also binds copper and has at least some oxidase activity similar to that of ceruloplasmin. Other tissues synthesize intracellular ceruloplasmin-like proteins. The present report represents part of an effort to examine the hypothesis that CMGP is a copper transport protein in chondrocytes and to characterize the enzymatic activities of CMGP. These studies demonstrate that CMGP is the principal chondrocyte protein labeled by 67Cu in vitro and that the label is localized to the mitochondria, cytosol, and membrane fractions of sucrose gradients, suggesting copper transport through the cell. In parallel experiments, [3H]leucine was incorporated into proteins corresponding to the subunits and fragments of CMGP, as described previously, and in a similar distribution among the subcellular fractions as labeled copper. Additionally, CMGP has oxidase and ferroxidase activities similar to those of ceruloplasmin.
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PMID:Studies of copper transport in cultured bovine chondrocytes. 791 77

Studies of mutants of the yeast Saccharomyces cerevisiae have led to the identification of genes required for high affinity iron uptake. Reduction of iron (III) outside the cell is accomplished by means of reductases encoded by FRE1 and FRE2, homologues of the gp91-phox component of the oxygen reductase of human granulocytes. High affinity iron (II) transport from the exterior to the interior of the cell occurs by means of a transport system that has not been molecularly characterized. However, the transport process requires the activity of a copper-containing oxidase encoded by FET3. The amino acid sequence of this protein resembles other multi-copper oxidases, including mammalian ceruloplasmin. High affinity copper uptake mediated by the copper transport protein encoded by CTR1 is required to provide the FET3 protein with copper, and thus copper uptake is indirectly required for ferrous iron uptake. These genetic elements of yeast and their relationships may be conserved in complex eukaryotic organisms.
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PMID:A genetic approach to elucidating eukaryotic iron metabolism. 798 80

To correlate genotype with response to early copper histidine therapy in Menkes disease, an X-linked disorder of copper transport, we performed mutational analysis in 2 related males who began treatment at the age of 10 days and prenatally at 32 weeks' gestation, respectively. A G to T transversion at the -1 exonic position of a splice donor site was identified, predicting a glutamine to histidine substitution at codon 724 of the Menkes copper-transporting ATPase gene. The Q724H mutation disrupts proper splicing and generates five mutant transcripts that skip from one to four exons. None of these transcripts is predicted to encode a functional copper transport protein. Copper histidine treatment normalized circulating copper and ceruloplasmin levels but did not improve the baseline deficiency of dopamine-beta-hydroxylase, a copper-dependent enzyme. At the age of 36 months, the first patient was living and had neurodevelopmental abilities ranging from 10 to 15 months. The second patient also showed delayed neurodevelopment and died of pulmonary complications at the age of 5 1/2 months. We conclude that early copper histidine therapy does not normalize neurological outcome in patients with the Q724H splicing mutation, and suggest that preservation of some residual Menkes ATPase activity may be a general prerequisite for significant clinical efficacy from such treatment.
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PMID:Early copper therapy in classic Menkes disease patients with a novel splicing mutation. 900 80

Previous studies have failed to explain the link between copper accumulation and abnormal caeruloplasmin expression in Wilson's disease. Furthermore, despite the isolation of a candidate gene for Wilson's disease, which predicts a defective copper transport protein, the localization of this putative protein and its relationship to the pathway involved in copper excretion and to caeruloplasmin remain unknown. We now present evidence that caeruloplasmin, the major plasma copper-carrying protein, is present in the liver in Wilson's disease, and thus that reduced circulating levels of the protein result from a post-translational defect in the secretory pathway. We have also identified a novel form of caeruloplasmin, molecular weight 125 kD, which we propose may act as the carrier for excretory copper into bile, since it is normally present in both liver and bile, although largely absent from serum, and undetectable in bile from Wilson's disease patients. The presence of this form of caeruloplasmin in Wilson's disease liver suggests that a related post-translational defect may also be responsible for its absence from bile in Wilson's disease. This study thus provides the first plausible explanation of a link between the defective copper excretion and the reduced plasma caeruloplasmin, which characterize Wilson's disease.
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PMID:Defective biliary copper excretion in Wilson's disease: the role of caeruloplasmin. 891 63


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