Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 evidence that the acute phase glycoproteins of plasma are synthesized by the liver parenchymal cells is critically examined, and is found to be inconclusive. Some evidence is cited which favors the reticulo-endothelial system (RES) in general, and Kupffer cells in particular, as the site of synthesis of these proteins: 1. The entire RES contains non-glycogenic periodic acid Schiff-positive substances. 2. The diseases which affect glycoprotein levels are also known to affect the function of the RES. 3. When the animal is subjected to stress, the RES function is initially depressed and then stimulated. A similar biphasic behavior is shown by plasma glycoprotein levels. 4. Adrenal cortico-steriods are the major regulators of the RES function and of the synthesis of acute phase proteins. Moreover, both are stimulated at low concentrations, and depressed at high concentrations of the hormone. Some of the glycoproteins of the acute phase (prothrombin, the third component of complement, haptoglobin, transferrin and ceruloplasmin) have defense-related functions. The others seem to participate in phenomena like detoxification, promotion of phagocytosis, wound healing, prevention of tissue injury by lysosomal enzymes, prevention of trauma and recovery from inflammation. It is proposed that the acute phase proteins, together with antibodies, form major components of the definse system, and the RES attempts to deal with injury by mobilization of increased amounts of these substances.
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PMID:The site of synthesis and functions of acute phase plasma proteins: close relationship with the reticulo-endothelial system. 19 83

Hormonally produced changes in the synthesis and secretion of the serum copper-containing protein caeruloplasmin were studied in primary cultures of rat liver parenchymal cells isolated by the collagenase-perfusion technique. A rabbit antibody directed against rat caeruloplasmin was used to immunoprecipitate labelled caeruloplasmin. Isolated liver cells synthesized and secreted caeruloplasmin over a period of 3 days. Synthesis and secretion of this protein was enhanced when cells were treated with dexamethasone. The accumulation of copper was also moderately enhanced with glucocorticoid treatment. Inclusion of adrenaline in the culture medium resulted in elevated incorporation of copper into newly synthesized caeruloplasmin as well as an increase in 64Cu-labelled caeruloplasmin in the culture medium. However, adrenaline did not seem to increase the secretion of 3H-labelled protein, despite the elevation in secreted 64Cu-caeruloplasmin. This may be due to a large increase in the intracellular pool of 64Cu caused by enhanced accumulation of this metal when adrenaline is included in the incubation medium. Enhanced copper accumulation was also seen when cells were treated with glucagon. Adrenaline-stimulated accumulation of 64Cu could be inhibited by including phenoxybenzamine, an alpha-adrenergic blocker, in the culture medium. Elevation of extracellular copper caused enhancement in the detection of labelled caeruloplasmin in the medium of cultured cells, probably owing to the ability of this metal to stabilize the protein.
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PMID:Hormonally produced changes in caeruloplasmin synthesis and secretion in primary cultured rat hepatocytes. Relationship to hepatic copper metabolism. 688 74

The effects of transition metals on nonenzymatic and ceruloplasmin catalyzed epinephrine oxidation were investigated by studying rates of epinephrine oxidation in purified buffers and in the presence of metal chelating agents. We found that epinephrine does not "autoxidize" in sodium chloride solutions prepared with deionized water that was further purified by chromatography over Chelex 100 resin prior to use. Epinephrine was oxidized rapidly in sodium chloride prepared with tap water (1.20 +/- 0.12 nmoles/min) or in deionized water (0.40 +/- 0.80 nmoles/min), but this oxidation was prevented by the addition of Desferal, a potent metal chelating agent. Epinephrine oxidation was enhanced upon the addition of ceruloplasmin, and this oxidation rate could be slowed, but not eliminated, by the addition of Desferal. If epinephrine solutions were preincubated for 72 hours with Desferal prior to ceruloplasmin addition, however, no oxidation was observed. Epinephrine was shown to form colored complexes with both iron and copper at pH 7.0. The Fe(III)-epinephrine complex was much more stable than was the Cu(II)-epinephrine complex. Oxygen consumption studies of ceruloplasmin catalyzed epinephrine oxidation showed that copper was a better promoter of epinephrine oxidation than was iron, suggesting that ceruloplasmin-catalyzed epinephrine oxidation results from adventitious copper bound to the purified enzyme. In light of these results, the physiological relevance of ceruloplasmin catalyzed oxidation of biogenic amines may be minor.
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PMID:The role of metals in the enzymatic and nonenzymatic oxidation of epinephrine. 849 1

Dietary copper deficiency was produced in Swiss albino mice and Sprague Dawley rats to determine the organ specificity of alterations in norepinephrine (NE) and dopamine (DA) concentrations and the relationship with organ copper levels. A 5-week dietary treatment was used, which started 1 week after birth for mice, initially via dams, and 3 weeks after birth for rats. Mice offspring (6 weeks of age) and rats (8 weeks of age) maintained on a copper-deficient (-Cu) treatment were compared with copper-adequate (+Cu) controls. Compared with +Cu animals, -Cu mice and rats were anemic and had low (<1% of +Cu) ceruloplasmin activities but normal body weights. The -Cu mice had organ copper concentrations ranging between 30% and 65% of +Cu values for eight organs studied, with the thymus being the least depleted. For -Cu rats, the range was 15% to 65%. Significant reductions in NE concentration were observed in the heart, pancreas, and spleen of -Cu mice. Elevated DA levels were observed in all organs except the brain. For -Cu rats, the NE level was lower in the heart and the DA level was higher in both the heart and spleen compared with +Cu rats. Dopamine elevation in the heart and spleen for both -Cu mice and rats was four- and fivefold higher, respectively. Adrenal catecholamine levels were only slightly changed by copper deficiency in mice or rats. Urinary levels of both NE and DA were higher in -Cu rats and mice. Plasma and heart tyrosine levels were not altered in -Cu mice. Elevated DA in -Cu rodents may be due to limiting dopamine-beta-monooxygenase. Higher urinary NE and lower organ NE may be due to a combination of decreased synthesis and enhanced turnover. The magnitude of decreased organ copper was not predictive of altered catecholamine pool size.
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PMID:Effect of dietary copper deficiency on the distribution of dopamine and norepinephrine in mice and rats. 1553 97

Human ceruloplasmin (hCP) is a multi-copper oxidase with ferroxidase and amine oxidase activities. Molecular dynamics simulation (MDS) and docking analysis of biogenic monoamines with ceruloplasmin explain the role of Asp1025, Glu935, Glu272, Glu232 and Glu230 together with the binding site water molecules (referred as conserved water molecules) in the stabilization of neurotransmitter (Serotonin, Norepinephrine and Epinephrine) molecules within the binding cavity of hCP. Conserved water molecules are found at specific positions interacting with the protein structures that have sequence similarity. The ethylamine side chain nitrogen atom (N1) of neurotransmitter molecules interacts with water molecules in the binding cavity formed by Asp1025, Glu935 and Glu232 residues. These residues form an acidic triad mimicking a substrate binding cavity. The hydroxyl groups attached to the catechol ring of epinephrine and norepinephrine have been stabilized by Asp230 and Asp232 residues. Data suggests that the recognition of biogenic amines mediates through the N+(amine) ...Asp1025-His1026-Cu_Cis-His path. The potential recognition path of biogenic monoamines to trinuclear copper cluster supported by active site water molecules (referred as conserved water molecules) is described in this report.
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PMID:Insights from molecular dynamics simulation of human ceruloplasmin (ferroxidase enzyme) binding with biogenic monoamines. 3183 58

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