Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antisera were raised in rabbits against histamine conjugated to human serum albumin (HSA) by the carbodiimide (ECDI) method. The specificity of the antisera was studied in a radioimmunoassay using 125I-protein A for detection of IgG binding. The HIS-HSA antisera reacted with histamine-HSA conjugates prepared by either the carbodiimide or diisocyanate coupling procedure, as well as with carbodiimide-prepared histamine-ferritin and histamine-ovalbumin conjugates. On the contrary, the antisera were unreactive with unconjugated HSA, ECDI-reacted HSA, or HSA conjugated to ethanolamine or pentylamine. Free unconjugated histamine significantly inhibited antibody binding to histamine-HSA and 50% inhibition of antibody binding (IC50) was recorded at 3 mM histamine concn. On a histamine molar concn basis a much lower inhibitory potency of free histamine was recorded, as compared to histamine-protein conjugates (IC50 = 3 X 10(-6) mM). This probably reflected amplification of antibody binding to the multivalent ligand, but possibly also that the protein carrier adds some common features to the antigenic determinant. Histidine, ornithine, glutamine, asparagine, sterylamine and several other amino acids lacked inhibitory effects. Histamine H1 and H2 receptor antagonists inhibited histamine binding to the histamine antibodies. The antagonists varied in their affinity for the histamine antibodies and 50% inhibition of antibody binding was recorded in the range of 1-50 mM concn of the antagonists. Comparing one H1 and one H2 antagonist (diphenhydramine and cimetidine, respectively) two of the sera were preferentially inhibited by cimetidine whereas the third serum seemed to be more prone to inhibition by diphenhydramine.
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PMID:Production and characterization of rabbit antibodies against histamine. 379 25

A novel extracellular mycobacterial enzyme was identified in the ruminant pathogen Mycobacterium paratuberculosis. The enzyme was capable of mobilizing iron from different sources such as ferric ammonium citrate, ferritin, and transferrin by reduction of the metal. The purified reductase had a calculated Mr of 17,000, was sensitive to proteinase K treatment, and had an isoelectric point of pH 9. Analysis of the amino acid composition revealed glycine, serine, asparagine (or aspartic acid), and glutamine (or glutamic acid) as the most frequently occurring residues. Enzymatic activity was highest at 37 degrees C and between pH 5 and 10. The calculated Km and Vmax for ferric ammonium citrate were 0.213 mM and 0.345 mM min(-1) mg(-1), respectively. Using a specific antireductase antibody in immunoelectron microscopy, we were able to detect the enzyme associated with intracellular mycobacteria in naturally M. paratuberculosis-infected bovine tissue. We prepose that the reductase of M. paratuberculosis represents an alternative strategy of mycobacteria to mobilize ferric iron and discuss its potential role in bacterial evasion of intracellular defense mechanisms.
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PMID:Identification and characterization of a novel extracellular ferric reductase from Mycobacterium paratuberculosis. 945 31

Ferritin, an iron-binding protein, was purified from the larval hemolymph of the wax moth, Galleria mellonella by KBr density ultracentrifugation and FPLC (Superose 6). The iron content of ferritin was determined by atomic emission spectroscopy and Ferene S stain. Native molecular mass of ferritin was estimated as 630 kDa. SDS-PAGE revealed that the ferritin consists of two major polypeptides of 26 and 32 kDa and one minor polypeptide of 30 kDa. An isoelectric point of ferritin was measured to be approximately 7.3 and only the 32-kDa subunit is glycosylated. The ferritin contains large amounts of lysine, glutamine, glutamic acid and leucine but tryptophan was not detected. Electron microscopic examination of negatively stained preparations showed an 11-nm particle in external diameter and 7-nm iron core. Ferritin is present in both the ovary and testis. Localization of ferritin by immunoelectron microscopy in ovary and testis revealed that the gold particles were located in vitelline membrane and yolk granules but not in follicular epithelium of ovary. In the testis, the gold particles were located in testicular fluid and lumen of vas deferens.
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PMID:Characterization and immunological analysis of ferritin from the hemolymph of Galleria mellonella. 1142 20

We are interested in the determinants that specify the structure of antiparallel coiled coils. Antiparallel coiled coils often contain alanine as an important interfacial packing residue; structures containing alanine at certain well-defined positions in the heptad-repeating unit are referred to as Alacoils. Two types have been identified, containing alanine at either the g position of the heptad repeating unit (defined as the d position in the Richardson nomenclature), referred to as a rop-like Alacoil, or the e position (a position in the Richardson nomenclature), referred to as a ferritin-like Alacoil. The Lac repressor tetramerization domain forms an antiparallel four-chain coiled coil, which falls into the second class of Alacoils based on recent crystal structures. The role of alanine in such structures has not yet been explored experimentally. We test the importance of alanine at the e positions on the oligomeric state and stability of the isolated coiled-coil domain of Lac repressor by testing the effect of mutations at this position. We find that mutation to leucine is tolerated and its moderately stabilizing effect is most likely a consequence of plasticity of this motif. The effects on stability of the mutations to either serine or glutamine can be largely accounted for by helix propensity differences between these residues and alanine. The ability of the helices to adjust to such mutations, while maintaining the basic fold of this coiled coil, was further tested by making the same changes at the more highly exposed g position. Leucine at the g positions also causes an increase in stability, presumably by subtle rearrangement of the helices to allow partial desolvation of this side-chain.
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PMID:Exploring the role of alanine in the structure of the Lac repressor tetramerization domain, a ferritin-like Alacoil. 1195 12

The influence of iron deposits on T2 values and the content of metabolites in the brain of three patients with DNA proved pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome) was studied. An eye-of-the-tiger sign, a typical MR finding for PKAN, was observed in two patients with the same mutation. A hypointensive lesion in a whole globus pallidus was observed in the third patient with the additional mutation. T2 values in the globus pallidus of the patients were about 40% shorter than in controls (71/48 ms in controls vs. patients), which corresponds to the increase of Fe concentration based on the ferritin basis from 17 mg for controls to 48 mg (100 g wet brain weight) in PKAN patients. 1H MR spectroscopy (MRS) has mainly been used to describe neuronal damage represented by decreased NAA (6.4 mmol vs. 9 mmol) and Cr/PCr (7.0 mmol vs. 9.8 mmol) concentrations in the basal ganglia region of the patient group to controls; MRS is much more case-sensitive and describes individual development of the disease as demonstrated in the difference between the spectra of typical PKAN patients (1, 2), and the patient (3) with atypical PKAN development. Any significant changes of metabolite concentration with the exception glutamine, glutamate and GABA were found in the white matter.
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PMID:MR relaxometry and 1H MR spectroscopy for the determination of iron and metabolite concentrations in PKAN patients. 1556 11

The distinction between positive and negative training adaptation is an important prerequisite in the identification of any marker for monitoring training in athletes. To investigate the glutamine responses to progressive endurance training, twenty healthy males were randomly assigned to a training group or a non-exercising control group. The training group performed a progressive (3 to 6 x 90 minute sessions per week at 70 % V.O (2max)) six-week endurance training programme on a cycle ergometer, while the control group did not participate in any exercise during this period. Performance assessments (V.O (2max) and time to exhaustion) and resting blood samples (for haemoglobin concentration, haematocrit, cortisol, ferritin, creatine kinase, glutamine, uric acid and urea analysis) were obtained prior to the commencement of training (Pre) and at the end of week 2, week 4 and week 6. The training group showed significant improvements in time to exhaustion (p < 0.01), and V.O (2max) (p < 0.05) at all time points (except week 2 for V.O (2max)), while the control group performance measures did not change. In the training group, haemoglobin concentration and haematocrit were significantly lower (p < 0.01) than pretraining values at week 2 and 4, as percentage changes in plasma volume indicated a significant (p < 0.01) haemodilution (+ 6 - 9 %) was present at week 2, 4 and 6. No changes were seen in the control group. In the training group, plasma glutamine (week 2, 4 and 6), creatine kinase (week 2 and 4), uric acid (week 2 and 4) and urea (week 2 and 4) all increased significantly from pretraining levels. No changes in cortisol or ferritin were found in the training group and no changes in any blood variables were present in the control group. Plasma glutamine was the only blood variable to remain significantly above pretraining (966 +/- 32 micromol . 1 (-1)) levels at week 6 (1176 +/- 24 micromol . 1 (-1); p < 0.05) The elevation seen here in glutamine levels, after 6 weeks of progressive endurance training, is in contrast to previous reports of decreased glutamine concentrations in overtrained athletes. In conclusion, 6 weeks of progressive endurance training steadily increased plasma glutamine levels, which may prove useful in the monitoring of training responses.
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PMID:Monitoring 6 weeks of progressive endurance training with plasma glutamine. 1702 35

Studies suggest that disturbances of amino acid metabolism and cellular iron regulation are important mechanisms underlying manganese (Mn) neurotoxicity, although the targets underlying these disturbances are poorly defined. Using the AF5 neural-derived cell line, which displays GABAergic properties, we showed that Mn significantly increased glutamate release to 174%-214% of that of the control and that the effects of Mn exposure on the metabolism of glutamate, glutamine, alanine, and GABA resembled the effects of fluorocitrate, an inhibitor of aconitase, but not the effects of other toxicants including paraquat, rotenone, or 3-nitropropionic acid. Consistent with this, Mn inhibited aconitase activity in AF5 cells, resulting in a 90% increase in intracellular citrate; an in vitro assay revealed that m-aconitase was significantly more sensitive to inhibition by Mn than was c-aconitase. RNA mobility shift assay and Western blot showed that Mn treatment caused c-aconitase to be converted to iron regulatory protein 1 (IRP1) and increased the abundance of IRP2, leading to reduced H-ferritin expression, increased transferrin receptor expression, and increased uptake of transferrin. To determine the relative contributions of IRP1 and IRP2 in mediating the effects of Mn on iron homeostasis, we exposed transgenic fibroblasts lacking either c-aconitase/IRP1 or IRP2 to Mn. Manganese exposure minimally altered ferritin levels in cells possessing only c-aconitase/IRP1, whereas cells possessing only IRP2 showed a robust decrease in ferritin, indicating a dominant role of IRP2 in Mn-induced alteration of iron homeostasis. Together, these results demonstrate that m-aconitase is an important target of Mn and thatMn-induced alteration of iron homeostasis is mediated predominantly through IRP2.
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PMID:Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells. 1746 37

Renal Fanconi syndrome developed rapidly in a 3-year-old Moroccan girl with established lysinuric protein intolerance. She was hospitalized because of lowered consciousness, uncoordinated movements and hepatosplenomegaly after a febrile period. Laboratory investigations revealed plasma ammonia 270 micromol/L (normal <70 micromol/L), ferritin 159 micromol/L (normal 2-59 micromol/L), LDH 1180 U/L (normal 26-534 U/L). LPI was diagnosed based on the findings of reduced plasma ornithine, arginine and lysine, and an increased level of glutamine. Urinary orotic acid (645 micromol/mmol creatinine; normal <3.6) was strongly increased. A defect in the SLC7A7 amino acid transporter was established (homozygous c.726G > A mutation). Detailed renal function tests including an acid challenge test, bicarbonate loading, and tubular maximal reabsorption of glucose showed complex tubular dysfunction. No evidence of respiratory chain defects was found in muscle or kidney tissue. No morphological abnormalities were demonstrated in the mitochondria. Ultrastructural analysis of proximal tubular cells showed vacuolization and sloughing of the apical brush border (Fig. 1). Renal involvement in LPI has only been described in a few reports; however, no detailed studies of the renal acidification mechanism were performed. Our patient had evidence of a full-blown Fanconi syndrome. Surprisingly, a metabolic acidosis was found with a moderately increased serum anion gap combined with repeatedly normal plasma organic acid values. This finding is in contrast with the diagnosis of renal tubular acidosis. Patients with hyperlysinaemia have a similar heavy load on the renal tubules; they never develop a renal Fanconi syndrome. Therefore, we consider the intratubular accumulation of lysine an unlikely candidate for the development of the renal Fanconi syndrome.
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PMID:Renal Fanconi syndrome with ultrastructural defects in lysinuric protein intolerance. 1753 Apr 37

Ferritin is a widespread iron mineralizing and detoxification protein that stores iron as a hydrous ferric oxide mineral core within a shell-like structure of 4/3/2 octahedral symmetry. Iron mineralization is initiated at dinuclear ferroxidase centers inside the protein where Fe(2+) and O(2) meet and react to form a mu-1,2-peroxodiferric intermediate that subsequently decays to form mu-oxo dimeric and oligomeric iron(III) species and ultimately the mineral core. Several types of channels penetrate the protein shell and are possible pathways for the diffusion of iron and dioxygen to the ferroxidase centers. In the present study, UV/visible and fluorescence stopped-flow spectrophotometries were used to determine the kinetics and pathways of Fe(2+) diffusion into the protein shell, its binding at the ferroxidase center and its subsequent oxidation by O(2). Three fluorescence variants of human H-chain ferritin were prepared in which Trp34 was introduced near the ferroxidase center. They included a control variant no. 1 (W93F/Y34W), a "1-fold" channel variant no. 2 (W93F/Y34W/Y29Q) and a 3-fold channel variant no. 3 (Y34W/W93F/D131I/E134F). Anaerobic rapid mixing of Fe(2+) with apo-variant no. 1 quenched the fluorescence of Trp34 with a rate exhibiting saturation kinetics with respect to Fe(2+) concentration, consistent with a process involving facilitated diffusion. A half-life of approximately 3 ms for this process is attributed to the time for diffusion of Fe(2+) across the protein shell to the ferroxidase center. No fluorescence quenching was observed with the 3-fold channel variant no. 3 or when Zn(2+) was prebound in each of the eight 3-fold channels of variant no. 1, observations indicating that the hydrophilic channels are the only avenues for rapid Fe(2+) access to the ferroxidase center. Substitution of Tyr29 with glutamine at the entrance of the "1-fold" hydrophobic channel had no effect on the rate of Fe(2+) oxidation to form the mu-1,2-peroxodiferric complex (t(1/2) approximately 38 ms), a finding demonstrating that Tyr29 and, by inference, the "1-fold" channels do not facilitate O(2) transport to the ferroxidase center, contrary to predictions of DFT and molecular dynamics calculations. O(2) diffusion into ferritin occurs on a time scale that is fast relative to the millisecond kinetics of the stopped-flow experiment.
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PMID:Facilitated diffusion of iron(II) and dioxygen substrates into human H-chain ferritin. A fluorescence and absorbance study employing the ferroxidase center substitution Y34W. 1905 59

Density functional theory optimizations have been conducted on structures of complexes of Fe(2+) with (H(2)O)(n) (n = 0-3) in three-residue models of binding sites A and B of the ferroxidase center of bullfrog M ferritin. Each site is modeled by the full structures of its three active amino acids. The potential surface at each site in the presence of water molecules is complex; coordination numbers of iron from three to six are seen. Water contributes to the complexity through its ability to hydrogen bond, to coordinate to iron, and to displace the neutral ligands glutamine and histidine. Intrinsic differences are noted at each site; at site B, the most stable complexes are found to favor tetracoordinate iron, while pentacoordination is preferred at site A in the two- and three-water complexes. While each incremental addition of a water molecule results in increased stability, successive binding energies are found to decrease.
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PMID:DFT comparison of Fe2+ hydration in the binding sites of the ferroxidase center of bullfrog M ferritin. 1919 73


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