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 ferroxidase II protein from human serum is large and structurally complex. It possesses protein-bound lipid and copper components which are essential for the maintenance of its catalytic activity. Treatment of ferroxidase II with 8 M urea, 6 M guanidine hydrochloride, or 6 M guanidine hydrochloride and alkylation does not result in the dissociation of the enzyme into subunits. However, treatment with sodium dodecyl sulfate results in the dissociation of ferroxidase II into two nonidentical subunits, designated S-I and S-II. S-I contains little phospholipid, cholesterol, or copper and has a molecular weight of 3.8-3.9 X 10(5). In contrast, S-II contains bound phospholipid, cholesterol, and copper and has a molecular weight of 2.2-2.4 X 10(5). The lipid compositon of S-II is identical with the native enzyme. Sodium dodecyl sulfate-free S-I exhibits no ferroxidase activity. Immediately following removal of sodium dodecyl sulfate, S-II exhibits ferroxidase activity but S-II rapidly loses its activity in the absence of S-I. The separated subunits spontaneously reassociate upon removal of the sodium dodecyl sulfate to yield a fully active enzyme which chemically appears identical with native ferroxidase II. Furthermore, the reconstituted enzyme is stable. Both native and reconstituted ferroxidase II may be stored at 4 degrees C for 6 weeks without any loss in activity. This suggests that S-II, the copper and lipid-containing subunit, is the catalytic subunit and that S-I is essential for the stabilization of the enzymic activity of S-II. These results provide insight into the molecular structure and chemical composition of ferroxidase II and suggest that the complete native structure of ferroxidase II is required for the maintenance of i-s functional integrity.
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PMID:Dissociation and reconstitution of human ferroxidase II. 1 23

To understand the role of copper in initiating protein alterations in rheumatoid arthritis (RA) as reported previously, concentrations of copper anc caeruloplasmin were determined in RA patients. The mean copper concentration of the RA population examined was 24.8 mumol/l (157.5 mug/100 ml), and the mean caeruloplasmin concentration in this RA population was 45.52 mg/100 ml. These values are not different from those reported by previous workers. However, when the RA population was divided into three groups according to sex and oestrogen therapy it was found that caeruloplasmin and copper concentrations in the group of female RA patients on oestrogens was significantly different from other groups (P less than 0.001). A highly significant (P less than 0.01) positive correlation was obtained between copper and caeruloplasmin concentrations (r = 0.91). Concentrations of copper and caeruloplasmin failed to explain the low sulphydryl content of plasma which was observed to be independent of these two parameters. Increased alpha2-globulin concentration, which was refractory to chrysotherapy but 'finger-printed' with a pure preparation of caeruloplasmin in electrophoresis, along with the absence of Kayser-Fleischer rings, supports the contention that copper is not present in a free ionic state in RA patients. This study shows that only a concurrent oestrogen therapy raises copper and caeruloplasmin concentration significantly in a female RA population. Past investigators appear to have overlooked this fact, and it could be that a disproportionate sex distribution (more female rheumatoid arthritics) could cause misleading results in RA studies. The role of oestrogens, copper, and caeruloplasmin in causing exacerbation of RA symptoms is discussed.
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PMID:Significance of plasma copper and caeruloplasmin concentrations in rheumatoid arthritis. 4 78

Twenty-six patients with primary lung cancer were studied in whose blood we found a significant increase in the levels of copper, ceruloplasmin, lactic-dehydrogenase and alpha 2-globulins. The role of copper in pulmonary cancerogenesis is discussed.
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PMID:Serum copper, ceruloplasmin, lactic-dehydrogenase and alpha 2-globulin in lung cancer. 9 May 32

Nine samples of human ceruloplasmin [iron(II):oxygen oxidoreductase; EC 1.16.3.1] prepared by different procedures have been examined for heterogeneity; gel electrophoresis showed that seven contained a number of components with molecular weights ranging from 20,000 to 130,000, and two contained largely a single component of molecular weight 130,000. Digestion of a single-component preparation with plasmin produced fragments with molecular weights similar to those found in the multicomponent preparations. Amino-terminal analysis, peptide mapping, and amino acid analysis showed that plasmin digestion generated a fragment of 20,000 molecular weight, which corresponded to a component present in a multicomponent ceruloplasmin preparation. The 20,000 molecular weight fragment appears to correspond to the so-called alpha-subunit or L-chain of human ceruloplasmin. Chemical evidence is thus provided that ceruloplasmin is a single-chain protein and that the so-called subunits are fragments. The 20,000 molecular weight fragment contains a single cysteine; amino acid sequence studies have shown that the sequence in the vicinity of this residue is similar to that around the single cysteine residue in plant plastocyanins and bacterial azurins, which are small, blue, copper-containing proteins.
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PMID:Chemical evidence that proteolytic cleavage causes the heterogeneity present in human ceruloplasmin preparations. 14 97

The cellular immune response of a 17-year-old decerebrate male with acquired zinc deficiency was studied. He had been fed a commercial formula which contained 7.6 mg zinc per kilogram. His caloric intake had been inadequate as judged by his cachexia. A detailed pretreatment nutritional assessment (five separate observations) which included total serum protein and globulins, albumin, folate, vitamins A, B2, C, ceruloplasmin, and plasma zinc, copper, iron, and total iron binding capacity revealed that the patient was deficient only in zinc and calories. His plasma zinc was 41 +/- 5 microgram/d1 compared with our laboratory norm of 89 +/- 9 microgram/d1 for young adult males. Cellular immunity was assessed by delayed skin reactivity to dinitrochlorobenzene and by in vitro lymphocyte transformation studies. Before zinc therapy the patient rendered a negative skin reaction to dinitrochlorobenzene, and the ability of his lymphocytes to undergo blast transformation in response to mitogen stimulation was significantly depressed with a stimulation index of 4.7 +/- 0.8 as compared with 139.1 +/- 77.3 for controls. Within 3 weeks after zinc therapy (22.7 mg zinc per day) he demonstrated a positive delayed skin reaction to dinitrochlorobenzene and a normal lymphocyte response stimulation index = 205.5 +/- 42.6 versus 199.3 +/- 58.2 for control). In addition, a pretreatment facial seborrhea and a decubitus ulcer rapidly healed.
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PMID:Abnormal cellular immune responses during acquired zinc deficiency. 15 94

It was found in experiments on male albino rats that hypophysectomy was accompanied by an increase of potassium (on account of its accumulation in the mitochondria, nuclei and the microsomes) and copper in the liver. At the same time there was an increase in this organ of tha activity of Mg-2+-Na-+-K-+-ATPase and Mg-+-ATPase, and also a rise of ceruloplasmin activity in the blood serum. STH and TTH restored the sodium content to the normal and increased potassium level in the liver of hypophysectomized rats. ACTH and STH increased copper content in the hepatic tissue and normalized the activity of ceruloplasmin in the blood. All the hormones used promoted normalization of ATP-ase activity.
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PMID:[The effect of STH, TTH and ACTH on several aspects of copper, sodium and potassium metabolism in the livers of hypophysectomized white rats]. 16 74

1. Male rats were maintained from wearing to between 4 and 16 weeks of age on a semisynthetic diet which was deficient in copper. 2. Methyl esters of fatty acids from adipose tissue of the rats were analysed by gas-liquid chromatography and the desaturase activity of liver microsomes, with [1-14C]=stearic acid as the substrate, was determined. Liver and plasma Cu concentration, cytohrome c oxidas (EC 1.9.3.I) activity and caeruloplasmin activity were determined as indices of Cu status. 3. Cu deficiency was associated with decreased mono-unsaturated:saturated ratios for C16 and C18 fatty acids from subcutaneous adipose tissue and decreased desaturase activity for liver microsomes. When Cu-deficient rats were given free access to the Cu-adequate diet or were injected intraperitoneally with an aqueous solution of CuSO4, that is, when the animals were related with Cu, the indices of Cu status, and desaturase activity for liver microsomes returned to values found in control animals. 4. When Cu or a Cu-chelator (Neocuproine) was added to microsomes, there was no effect on the activity of the desaturase enzyme system; the stability of the desaturase was not affected by Cu. 5. These results are indicative of an involvement of Cu in the desaturase reaction. It is suggested that the site of this involvement could be the terminal component of the microsomal electron transport chain.
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PMID:Effect of dietary copper deficiency. in the rat on fatty acid composition of adipose tissue and desaturase activity of liver microsomes. 16

The blood, spleen and liver of mice were examined by means of electron spin resonance (e.s.r.), throughout the course of myeloid leukaemia induced by intravenous injection of leukaemic spleen cells. In blood, marked increases in the concentrations of iron transferrin and ceruloplasmin occurred within the first 3 days after injection. In the spleen, changes in the concentrations of paramagnetic copper and iron complexes were detectable by about the 5th day, before any measurable splenic enlargement, whilst in the liver changes were detectable by about the 8th day. The changes occurring in blood, spleen and liver during the development of leukaemia appear to be related and they are discussed in terms of iron transport.
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PMID:Electron spin resonance study of changes during the development of a mouse myeloid leukaemia. I. Paramagnetic metal ions. 16 66

1. The reaction of nitric oxide with oxidized and reduced ascorbate oxidase (L-ascorbate: oxygen oxidoreductase, EC 1.10.3.3) has been investigated by optical absorption measurements and electron paramagnetic resonance, and the results are compared with those of ceruloplasmin. 2. Upon anaerobic incubation of oxidized ascorbate oxidase with nitric oxide a decrease of the absorbance at 610 nm is found, which is due to an electron transfer from nitric oxide to Type-1 copper. 3. In the presence of nitric oxide the EPR absorbance of ascorbate oxidase decreases and shows predominatly a signal with characteristics of Type-2 copper (g parallel = 2.248; A parallel = 188 G), whereas the type-1 copper signal has vanished. 4. Comparison of the intensities of the EPR signals before and after NO-treatment points to the presence of one Type-2 and three Type-1 copper atoms per molecule of ascorbate oxidase. 5. It is shown that the changes in the optical and the EPR spectrum of ascorbate oxidase induced by nitric oxide are reversible. No difference in enzymic activity is found between the native enzyme and the NO-treated enzyme after removal of nitric oxide.
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PMID:The interaction of nitric oxide with ascorbate oxidase. 17 Sep 67

Binuclear cupric ion clusters have been established in: human ceruloplasmin, hemocyanin, and mushroom tyrosinase. Substantial evidence makes it very probable that fungal laccase and zucchini ascorbate oxidase contain this cluster. Some evidence makes it possible that copper clusters function in the catalytic cycles of cytochrome oxidase (mammalian) and dopamine-beta-hydroxylase. These studies throw light on the criteria which must be employed to establish the existence of functional binuclear copper clusters in enzymes: (1) Stoichiometric Criteria: binding of O2 and CO with Cu/ligand = 2; redox titrations with n = 2; (2) Physical and Chemical Criteria: magnetic evidence of diminished paramagnetism of cupric centers, EPR evidence of broadened or absent absorptions, EPR evidence of magnetic dipolar interactions among cupric ions; absorption bands characteristic of Cu(II)-Cu(II) complexes; laser resonance raman scattering characteristic of peroxidic dioxygen in the oxyforms.
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PMID:Binuclear copper clusters as active sites for oxidases. 18 78


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