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)

In addition to copper bound to ceruloplasmin and to albumin, there is a third small fraction of copper in human serum that is bound to amino acids. The amino acid-bound fraction of copper is in equilibrium with albumin-bound copper, and both fractions are probably in equilibrium with ionic copper. Of the 23 amino acids that are known to be in human serum, a substantial number were shown (in physiological concentrations) to compete effectively with albumin for the binding of copper. In this respect, histidine had the most marked effect followed by glutamine, threonine, cystine, and others. The effect of the combined presence of 23 amino acids on the state of copper in human serum could not be explained on the basis of their individual abilities to compete with albumin for the binding of copper. It is suggested that copper may also be present in serum in the form of mixed amino acid-copper complexes consisting of one atom of copper and two different amino acids. Under normal conditions, histidine is the amino acid primarily involved in the formation of mixed amino acid-copper complexes in serum. In combination with histidine and copper, threonine, glutamine, and asparagine are the other amino acids that are most likely to be the third members of these mixed complexes. The first binding site for copper on human albumin is different from subsequent ones in that its binding affinity to copper is much higher. We propose that the amino acid-bound fraction of copper in serum may have a physiological role in the biological transport of copper.
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PMID:The state of copper in human serum: evidence for an amino acid-bound fraction. 602 Dec 11

Workers exposed to naphtha, tungsten, vanadium, cobalt and titanium exhibited decreased activity of asparagine and alanine aminotransferase, cholinesterase and ceruloplasmin in blood serum, as compared to controls. Activity of lactic acid dehydrogenase was not changed significantly. It might be surmised that absorption of metals and naphtha exhibits inhibitory properties in relation to the enzymes determined.
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PMID:[Effect of low concentrations of metals and benzin on serum enzyme activity]. 666 96

In those chronically exposed to manganese the activity of alanine aminotransferase (ALAT), asparagine aminotransferase (AspAT), lactate dehydrogenase (LDH), cholinesterase (ChE) and ceruloplasmin (CPL) was determined. As compared with the control group, only enzymatic activity was statistically decreased. Thus, determination of the mentioned enzymes in blood serum is of little value for evaluation of an early stage of manganese toxic effects.
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PMID:[Usefulness of various enzyme tests in the evaluation of the effects of chronic exposure to manganese and iron]. 688 56

We have examined the kinetics of binding and uptake of iodinated glycoproteins and glycopeptides bearing terminal Gal or GalNAc moieties in an isolated rat hepatocyte system. Asparagine-linked, triantennary complex oligosaccharides with three terminal Gal residues are endocytosed with the same kinetics as asialo-orosomucoid, whereas biantennary, complex oligosaccharides with one or two terminal Gal residues are not endocytosed Glycopeptides bearing as few as four O-glycosidically-linked Gal beta 1, 3GalNAc or GalNAc moieties are also rapidly endocytosed, while glycopeptides with one or two more closely spaced moieties are not endocytosed. All the endocytosable glycoproteins and glycopeptides have similar apparent dissociation constants and a similar number of binding sites on the surface of the intact hepatocyte. The ligand-binding properties of the receptor in the plasma membrane of intact cells differ from those of the solubilized receptor, suggesting that interaction with other as yet undefined cellular components confers the ability to discriminate among closely related oligosaccharide structures. This is consistent with a model in which only glycopeptides bearing terminal Gal or GalNAc residues that fall within a restricted spatial relationship can induce a conformational alteration in the receptor which is required for uptake to occur. The endocytosis of a number of glycoproteins such as human asialo-ceruloplasmin can be accounted for by the presence of a single, complex oligosaccharide with the appropriate structure.
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PMID:Galactose and N-acetylgalactosamine-specific endocytosis of glycopeptides by isolated rat hepatocytes. 744 75

Site-directed mutagenesis was performed on a set of six aspartate residues of Fet3, the multicopper ferroxidase involved in high-affinity iron transport in Saccharomyces cerevisiae, in order to comprehend the molecular determinants of the protein function. Asp312, Asp315, Asp319 and Asp320 were predicted by homology modelling to be located in a negatively charged surface-exposed loop of the protein. Other two aspartate residues (Asp278 and Asp279) are placed close to the type 1 copper- and iron-binding sites, possibly linking these sites to the negatively charged region. In vivo results showed that mutation of Asp319 and Asp320 to yield D319N and D320N derivatives strongly impairs the ability of the yeast to grow under iron-limiting conditions. In particular, substitution of Asp320 with asparagine essentially abolished the Fet3-dependent iron transport activity. All other mutants (D278Q, D279N, D312N and D315I) behaved essentially as the wild-type protein. The electron paramagnetic resonance spectrum of the soluble forms of D319N and D320N showed significant changes of the copper sites' geometry in D319N but not in D320N. At variance with the membrane-bound forms, soluble D319N and D320N derivatives were highly susceptible to proteolytic degradation, suggesting that replacement of Asp319 or Asp320 locally modifies the structure of Fet3, making the protein sensitive to proteolysis when it is not protected by the membrane environment. In turn, this might be evidence of a shielding role of the permease Ftr1, which could interact with Fet3 at the level of the aspartate-rich negatively charged region.
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PMID:Specific aspartate residues in FET3 control high-affinity iron transport in Saccharomyces cerevisiae. 1603 72

Hypoxic preconditioning reprogrammes the brain's response to subsequent H/I (hypoxia-ischaemia) injury by enhancing neuroprotective mechanisms. Given that astrocytes normally support neuronal survival and function, the purpose of the present study was to test the hypothesis that a hypoxic preconditioning stimulus would activate an adaptive astrocytic response. We analysed several functional parameters 24 h after exposing rat pups to 3 h of systemic hypoxia (8% O2). Hypoxia increased neocortical astrocyte maturation as evidenced by the loss of GFAP (glial fibrillary acidic protein)-positive cells with radial morphologies and the acquisition of multipolar GFAP-positive cells. Interestingly, many of these astrocytes had nuclear S100B. Accompanying their differentiation, there was increased expression of GFAP, GS (glutamine synthetase), EAAT-1 (excitatory amino acid transporter-1; also known as GLAST), MCT-1 (monocarboxylate transporter-1) and ceruloplasmin. A subsequent H/I insult did not result in any further astrocyte activation. Some responses were cell autonomous, as levels of GS and MCT-1 increased subsequent to hypoxia in cultured forebrain astrocytes. In contrast, the expression of GFAP, GLAST and ceruloplasmin remained unaltered. Additional experiments utilized astrocytes exposed to exogenous dbcAMP (dibutyryl-cAMP), which mimicked several aspects of the preconditioning response, to determine whether activated astrocytes could protect neurons from subsequent excitotoxic injury. dbcAMP treatment increased GS and glutamate transporter expression and function, and as hypothesized, protected neurons from glutamate excitotoxicity. Taken altogether, these results indicate that a preconditioning stimulus causes the precocious differentiation of astrocytes and increases the acquisition of multiple astrocytic functions that will contribute to the neuroprotection conferred by a sublethal preconditioning stress.
ASN Neuro 2011 Jul 26
PMID:Pre-conditioning induces the precocious differentiation of neonatal astrocytes to enhance their neuroprotective properties. 2172 95

Asparagine deamidation occurs spontaneously in proteins during aging; deamidation of Asn-Gly-Arg (NGR) sites can lead to the formation of isoAsp-Gly-Arg (isoDGR), a motif that can recognize the RGD-binding site of integrins. Ceruloplasmin (Cp), a ferroxidase present in the cerebrospinal fluid (CSF), contains two NGR sites in its sequence: one exposed on the protein surface ((568)NGR) and the other buried in the tertiary structure ((962)NGR). Considering that Cp can undergo oxidative modifications in the CSF of neurodegenerative diseases, we investigated the effect of oxidation on the deamidation of both NGR motifs and, consequently, on the acquisition of integrin binding properties. We observed that the exposed (568)NGR site can deamidate under conditions mimicking accelerated Asn aging. In contrast, the hidden (962)NGR site can deamidate exclusively when aging occurs under oxidative conditions, suggesting that oxidation-induced structural changes foster deamidation at this site. NGR deamidation in Cp was associated with gain of integrin-binding function, intracellular signaling, and cell pro-adhesive activity. Finally, Cp aging in the CSF from Alzheimer disease patients, but not in control CSF, causes Cp deamidation with gain of integrin-binding function, suggesting that this transition might also occur in pathological conditions. In conclusion, both Cp NGR sites can deamidate during aging under oxidative conditions, likely as a consequence of oxidative-induced structural changes, thereby promoting a gain of function in integrin binding, signaling, and cell adhesion.
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PMID:Oxidation-induced structural changes of ceruloplasmin foster NGR motif deamidation that promotes integrin binding and signaling. 2436 63

Type 2 diabetes mellitus (T2DM) is associated with oxidative stress and perturbed iron metabolism. Serotransferrin (Trf) and ceruloplasmin (Cp) are two key proteins involved in iron metabolism and anti-oxidant defense. Non-enzymatic glycation and oxidative modification of plasma proteins are known to occur under hyperglycemia and oxidative stress. In this study, shotgun proteomics and 2H2O-based metabolic labeling were used to characterize post-translational modifications and assess the kinetics of Trf and Cp in T2DM patients and matched controls in vivo. Six early lysine (Amadori) and one advanced arginine glycation were detected in Trf. No glycation, but five asparagine deamidations, were found in Cp. T2DM patients had increased fractional catabolic rates of both Trf and Cp that correlated with HbA1c (p < 0.05). The glycated Trf population was subject to an even faster degradation compared to the total Trf pool, suggesting that hyperglycemia contributed to an increased Trf degradation in T2DM patients. Enhanced production of Trf and Cp kept their levels stable. The changes in Trf and Cp turnover were associated with increased systemic oxidative stress without any alteration in iron status in T2DM. These findings can help better understand the potential role of altered Trf and Cp metabolism in the pathogenesis of T2DM and other diseases.
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PMID:Increased serotransferrin and ceruloplasmin turnover in diet-controlled patients with type 2 diabetes. 2907 28