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)

Porphyria cutanea tarda (PCT) is characterized biochemically by excessive hepatic synthesis and urinary excretion of uroporphyrin I. Clinical evidence has implicated iron in the pathogenesis of PCT. The synthesis of the normally occurring isomer of uroporphyrin, namely uroporphyrin III, from porphobilinogen (PBG) requires two enzymes; uroporphyrinogen I synthetase and uroporphyrinogen III cosynthetase (COSYN). In the absence of COSYN only uroporphyrinogen I is formed. These experiments were designed to study the effect of iron on porphyrin biosynthesis in porcine and human crude liver extracts and to measure COSYN activity in the presence of iron.Mitochondria-free crude liver extracts were prepared in 0.25 m sucrose at pH 7.4 by centrifugation at 37,000 g. Preparations were incubated with either 0.2 mm amino-levulinic acid (ALA) or 0.1 mm PBG. The addition of ferrous ion (either from ferritin iron [4 mug/ml] and cysteine [6.7 mm] or ferrous ammonium sulfate [0.3 mm Fe] and cysteine) significantly increased the rate of uroporphyrin synthesis from either ALA or PBG. The predominant porphyrin synthesized in the presence of ferrous ion was uroporphyrin I whereas coproporphyrin III predominated in its absence. Orthophenanthroline blocked these effects of ferrous ion.To investigate the effect of ferrous ion on COSYN, crude liver extracts were incubated with ferrous ammonium sulfate (0.3 mm Fe) and cysteine (6.7 mm) and the COSYN activity of the incubates was assayed directly. In both porcine and human extracts ferrous ion caused marked inhibition of COSYN activity. Orthophenanthroline blocked the inhibitory effect.Inactivation of COSYN by heating resulted in marked enhancement of porphyrin synthesis from PBG. The sole product was uroporphyrin I.Thus, inactivation of COSYN results in accelerated synthesis of uroporphyrin I. This effect of ferrous ion provides a possible biochemical explanation for the excess production and excretion of uroporphyrin I in patients with PCT and the reversal of this defect by phlebotomy.
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PMID:The role of iron in the pathogenesis of porphyria cutanea tarda. An in vitro model. 464 Sep 47

1. Horse spleen apoferritin catalyses the oxidation of Fe(2+) to Fe(3+) with molecular O(2) as electron acceptor under conditions where a number of other proteins have no such effect. The product is similar to ferritin by a number of criteria. 2. The progress curve is hyperbolic and the increase in initial velocity is linear with increasing apoferritin concentration. With respect to Fe(2+) the reaction follows Michaelis-Menten kinetics. The pH-dependence of the reaction was determined between pH4.3 and 6.0. 3. Modification of both tryptophan residues/apoferritin subunit with 2-nitrophenylsulphenyl chloride does not affect either k(cat.) or K(m) for the oxidation. Neither does the guanidination of seven out of nine lysine residues/subunit, the modification of nine out of ten arginine residues/subunit with cyclohexanedione, or the nitration of one out of five tyrosine residues/subunit with tetranitromethane. 4. The carboxymethylation of two out of three cysteine residues/subunit and of one out of six histidine residues/subunit can be achieved with iodoacetic acid. This carboxymethylated apoferritin is completely inactive in Fe(2+) oxidation. 5. Apoferritin does not take up Fe(3+). It appears from these results that Fe(2+) is the form in which iron is taken up by ferritin in a reaction where the protein acts as an enzyme which traps the product in the interior of the protein shell.
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PMID:The catalytic activity of horse spleen apoferritin. Preliminary kinetic studies and the effect of chemical modification. 473 26

Inhibition by Zn(2+) of iron uptake by apoferritin at very low substrate concentrations is shown to be competitive. It is proposed that Zn(2+) competes with Fe(2+) for sites on the protein at which the oxidation of Fe(2+) is catalysed. Interpretation of titration data suggests there are two independent classes of binding site for Zn(2+) and several other cations. Sites in one such class are probably on the external surface of the apoferritin molecule. The catalytic binding sites are presumed to be internal and may involve histidine or possibly cysteine as ligands.
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PMID:The formation of ferritin from apoferritin. Inhibition and metal ion-binding studies. 479 13

1. Homogenates of rat liver, spleen, heart and kidney form lipid peroxides when incubated in vitro and actively catalyse peroxide formation in emulsions of linoleic acid or linolenic acid. 2. In liver, catalytic activity is distributed throughout the nuclear, mitochondrial and microsomal fractions and is present in the 100000g supernatant. Activity is weak in the nuclear fraction. 3. Dilute (0.5%, w/v) homogenates catalyse peroxidation over the range pH5.0-8.0 but concentrated (5%, w/v) homogenates inhibit peroxidation and destroy peroxide if the solution is more alkaline than pH7.0. 4. Ascorbic acid increases the rate of peroxidation of unsaturated fatty acids catalysed by whole homogenates of liver, heart, kidney and spleen at pH6.0 but not at pH7.4. 5. Catalysis of peroxidation of unsaturated fatty acids by the mitochondrial and microsomal fractions of liver is inhibited by ascorbic acid at pH7.4 but the activity of the supernatant fraction is enhanced. 6. Inorganic iron or ferritin are active catalysts in the presence of ascorbic acid. 7. Lipid peroxide formation in linoleic acid or linolenic acid emulsions catalysed by tissue homogenates is partially inhibited by EDTA but stimulated by o-phenanthroline. 8. Cysteine or glutathione (1mm) inhibits peroxide formation catalysed by whole homogenates, mitochondria or haemoprotein. Inhibition increases with increase of pH.
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PMID:Mechanisms of lipid peroxide formation in animal tissues. 596 63

During the last week of gestation of the fetal rat, the epithelium of the colon is rapidly remodeled. At 16 days a primitive stratified epithelium surrounds a small central lumen. Over the next 3 days, the main lumen extends narrow clefts down to the basal cell layer and small secondary lumina appear within the stratified epithelium between these clefts. At 19 and 20 days, secondary lumina enlarge but remain discrete; an infusion of cationic ferritin into the main lumen does not enter secondary lumina. During the 2 days prior to birth (21-22), the secondary lumina join the main lumen as superficial cells are sloughed, and the epithelium becomes simple columnar. Freeze-fracture replicas indicate that luminal and nonluminal membrane domains of epithelial cell plasma membranes are separated by continuous tight junctions throughout the conversion process. Cytochemical analysis of tissue slices from 16- to 22-day fetal colon demonstrated the appearance and segregation of two phosphatases on apical and basolateral membrane domains during epithelial conversion. Cysteine-sensitive pH 9.0 (alkaline) phosphatase activity was first detected along the luminal membranes of cells bordering both primary and secondary lumina at 18 days gestation and increased to a maximum at 20-21 days; weaker activity was present on basolateral membranes. Phosphatase activity at pH 8.0 also appeared at 18 days and increased thereafter, but was localized primarily on nonluminal membranes. At pH 8.0, reaction product appeared on both inner and outer sides of the membrane, and was only partially abolished by omission of K+ or addition of ouabain; thus the reaction may be only partially due to K+-dependent ATPase activity. Biochemical analysis of the cytochemical media confirmed the appearance of phosphatase activities at 18 days. Thus, plasma membrane phosphatase activities appear while the epithelium is still stratified, but are segregated to luminal and nonluminal membrane domains at the onset of activity. Segregation is maintained throughout the process of conversion of a simple columnar epithelium.
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PMID:Epithelial differentiation in the fetal rat colon. I. Plasma membrane phosphatase activities. 630 78

Ferritin was isolated from the spleen of sheep and found to contain an iron/protein content of 21 per cent. Electrophoretic behaviour on 6 per cent polyacrylamide gel revealed three protein bands of Rf values of 5.7, 19.3 and 76.1. Sheep ferritin has a molecular weight of about 475,000 daltons and is high in glutamic acid, leucine and aspartic acid and low in methionine and cysteine. Sheep ferritin is not crystallisable by 10 per cent cadmium sulphate and has an ultraviolet-visible spectrum similar to that of bovine ferritin. Anti (sheep) ferritin antibodies raised in rabbits showed a 57.1 per cent binding at a serum dilution of 1:800 and 30 per cent binding at a 1:12,800 dilution, in a titre determination using double antibody assay procedure.
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PMID:Isolation of sheep spleen ferritin. 647 7

The filamentous bacteriophage f1 can be transformed into a spherical particle (spheroid) or an intermediate shortened filament with a flared end (I-forms) by exposure to a chloroform-water interface at 22 or 4 degrees C, respectively. The protein composition of bacteriophage f1 spheroids and I-forms was examined by separating the proteins from the purified. [35S]cysteine-labeled particles by sodium dodecyl sulfate-urea-polyacrylamide gel electrophoresis. Quantitation of the radioactivity on the gels showed that I-forms and spheroids contain the same complement of minor coat proteins as do untreated f1 phage. This composition is unchanged after removal of the DNA, either by digestion with micrococcal nuclease or by centrifugation of the particles through CsCl density gradients, indicating that none of the minor coat proteins is held in the particles solely through an interaction with the DNA. We also examined the location of the A protein in I-forms by decoration with ferritin-conjugated antibodies and examination under the electron microscope and found that the A protein is located specifically at the flared end of the I-form particle, through which the DNA is extruded and at which contraction into spheroids begins. The implications of these results with regard to the orientation of the DNA within the capsid and the process of infection are discussed.
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PMID:Minor coat protein composition and location of the A protein in bacteriophage f1 spheroids and I-forms. 709 58

Ferritin from horse spleen was found to cause severe chromosome aberrations in cultured Chinese hamster ovary cells. Ferritin at 15 to 170 microgram/ml was clastogenic and at higher doses was cytotoxic. At comparable concentrations of protein or iron, neither apoferritin nor complexed iron was clastogenic. Sulfhydryl compounds glutathione and cysteine reduced the cytotoxic and clastogenic activities of ferritin. Physiological concentrations of glutathione may normally be sufficient to protect cells from damage. The reducing agent ascorbate had little protective effect. Chelating agents varied in their inhibitory activity: ethylenediaminetetraacetic acid (hexadentate) greater than nitrilotriacetic acid (tetradentate) greater than salicylate (bidentate). 2,2'-Bipyridyl enhance the chromosome-damaging action of ferritin while histidine did not markedly alter the frequencies of aberrations. Catalase and superoxide dismutase showed no inhibitory activity. The mechanism of DNA damage may involve reduction of Fe(III) in the ferritin core to Fe(II), followed by reoxidation of Fe(II) with possible formation of free radicals.
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PMID:Chromosome-damaging activity of ferritin and its relation to chelation and reduction of iron. 719 42

Light microscopy and transmission electron microscopy of thin sections and metal-shadowed specimens showed that the sheath of Leptothrix discophora SP-6 (ATCC 51168) is a tube-like extracellular polymeric structure consisting of a condensed fabric of 6.5-nm-diameter fibrils underlying a more diffuse outer capsular layer. In thin sections, outer membrane bridges seen to contact the inner sheath layer suggested that the sheath fabric was attached to the outer layer of the gram-negative cell wall. The capsular polymers showed an affinity for cationic colloidal iron and polycationic ferritin, indicating that they carry a negative charge. Cell-free sheaths were isolated by treatment with a mixture of lysozyme, EDTA, and N-lauroylsarcosine (Sarkosyl) or sodium dodecyl sulfate (SDS). Both Sarkosyl- and SDS-isolated sheaths were indistinguishable in microscopic appearance. However, the Mn-oxidizing activity of Sarkosyl-isolated sheaths was more stable than that of SDS-isolated sheaths. The Sarkosyl-isolated sheaths also contained more 2-keto-3-deoxyoctanoic acid and more outer membrane protein than SDS-isolated sheaths. The oven-dried mass of detergent-isolated sheaths represented approximately 9% of the total oven-dried biomass of SP-6 cultures; the oven-dried sheaths contained 38% C, 6.9% N, 6% H, and 2.1% S and approximately 34 to 35% carbohydrate (polysaccharide), 23 to 25% protein, 8% lipid, and 4% inorganic ash. Gas-liquid chromatography showed that the polysaccharide was an approximately 1:1 mixture of uronic acids (glucuronic, galacturonic, and mannuronic acids and at least one other unidentified uronic acid) and an amino sugar (galactosamine). Neutral sugars were not detected. Amino acid analysis showed that sheath proteins were enriched in cysteine (6 mol%). The cysteine residues in the sheath proteins probably provide sulfhydryls for disulfide bonds that play an important role in maintaining the structural integrity of the sheath (D. Emerson and W.C. Ghiorse, J. Bacteriol. 175:7819-7827, 1993).
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PMID:Ultrastructure and chemical composition of the sheath of Leptothrix discophora SP-6. 750 63

The control of cellular iron homeostasis involves the coordinate post-transcriptional regulation of ferritin mRNA translation and transferring receptor mRNA stability. These regulatory events are mediated by a soluble cytoplasmic protein, iron regulatory factor (IRF), which binds specifically to mRNA hairpin structures, termed iron-responsive elements (IREs), in the respective mRNAs. IRF is modulated by variations of cellular iron levels and exists as either an apo-protein or a [4Fe-4S]-cluster protein. The two conformations show distinct, mutually exclusive functions. High-affinity IRE binding is observed with the apo-form induced by iron deprivation, but is lost under high iron conditions when IRF is converted to the [4Fe-4S]-cluster form which shows cytoplasmic aconitase activity. Moreover, IRE binding is inactivated by the sulfhydryl-oxidizing agent diamide and fully activated in vitro by 2% 2-mercapto-ethanol, whereas alkylation of IRF inhibits IRE binding. In the present study, we analyzed each of the above features using site-directed mutants of recombinant human IRF. The results support the bifunctional nature of IRF. We conclude that cysteines 437, 503 and 506 anchor the [4Fe-4S]-cluster, and are essential to the aconitase activity. Mutagenesis changing any of the cysteines to serine leads to constitutive RNA binding in 0.02% 2-mercaptoethanol. Cysteine 437 is particularly critical to the RNA-protein interaction. The spontaneous or diamide-induced formation of disulfide bonds between cysteines 437 and 503 or 437 and 506, in apo-IRF, as well as its alkylation by N-ethylmaleimide, inhibit binding to the IRE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mutational analysis of the [4Fe-4S]-cluster converting iron regulatory factor from its RNA-binding form to cytoplasmic aconitase. 750 61


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