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PubMed1988

Siderophore containing 2,3-dihydroxybenzoic acid and threonine formed by Rhizobium trifolli.

An iron-binding compound was isolated from ethyl acetate extract of culture supernatant fluid of Rhizobium trifolii AR6 and was purified by iron-exchange chromatography. The compound was characterized by UV and IR. It contained 2,3-dihydroxy-benzoic acid and threonine and was accumulated during stationary phase of growth in iron-deficient media. Synthesis of the siderophore was repressed by FeCl3. In iron limited medium the compound promoted growth of R. trifolii strains.

Hydrogen-Ion Concentration↗
PubMed2006

Hemochromatosis and severe iron overload associated with compound heterozygosity for TFR2 R455Q and two novel mutations TFR2 R396X and G792R.

We report three mutations of transferrin receptor 2 (TFR2)--R396X (exon 9; nt 1186C-->T), R455Q (exon 10; nt 1364G-->A) and G792R (exon 18; nt 2374G-->A)--in a man of Scottish descent with hemochromatosis and severe iron overload. He was also heterozygous for the common HFE H63D polymorphism. The patient did not have coding region mutations in HAMP, FPN1, HJV or ALAS2. We conclude that this patient represents another example of hemochromatosis due to mutations of the gene encoding transferrin receptor 2.

Amino Acid Substitution↗
PubMed2005

[Simple method for precognition of drug interaction between oral iron and phenolic hydroxyl group-containing drugs].

In the present study, we devised a simple method for detecting the drug interaction between oral iron preparations and phenolic hydroxyl group-containing drugs, using the coloring reaction as indicator, due to the formation of complexes or chelates. In the method, oral iron preparations and test drugs in amounts as much as single dose for adults were added to 10 ml of purified water to make sample suspensions for testing. Thirty minutes after mixing an oral iron suspension and a test drug suspension, the change of color in the mixture was observed macroscopically and graded as 0 to 3, with a marked color change judged as grade 3 and no color change as grade 0. Screening of 14 test drugs commonly used orally was carried out. When using sodium ferrous citrate preparations as oral iron, 5 were classified as grade 3, 2 as grade 2, 4 as grade 1, and 3 as grade 0, respectively. To verify usefulness of the method, the interactions suggested by screening were pharmacokinetically assessed by measuring serum concentrations of the drug in mice. When a levodopa or droxidopa preparation, judged as grade 3 in screening, was concomitantly administered with an iron preparation, a significant reduction in bioavailability of the test drug was observed, indicating possible drug interaction between the test drug and oral iron. Combined administration of an acetaminophen preparation, judged as grade 1, and oral iron preparation showed no influence on the bioavailability of the test drug, implying no detectable interactions between them. In conclusion, the simple method devised in the present study is useful for precognition of drug interactions between oral iron preparations and phenolic hydroxyl group-containing drugs, and the drugs with a higher grade in screening may induce drug interactions with oral iron.

Acetaminophen↗
PubMed2000

Genes that modify the hemochromatosis phenotype in mice.

Hereditary hemochromatosis (HH) is a prevalent human disease caused by a mutation in HFE, which encodes an atypical HLA class I protein involved in regulation of intestinal iron absorption. To gain insight into the pathogenesis of hemochromatosis, we have bred Hfe knockout mice to strains carrying other mutations that impair normal iron metabolism. Compound mutant mice lacking both Hfe and its interacting protein, beta-2 microglobulin (B2m), deposit more tissue iron than mice lacking Hfe only, suggesting that another B2m-interacting protein may be involved in iron regulation. Hfe knockout mice carrying mutations in the iron transporter DMT1 fail to load iron, indicating that hemochromatosis involves iron flux through DMT1. Similarly, compound mutants deficient in both Hfe and hephaestin (Heph) show less iron loading than do Hfe knockout mice, indicating that iron absorption in hemochromatosis involves the function of Heph as well. Finally, compound mutants lacking Hfe and the transferrin receptor accumulate more tissue iron than do mice lacking Hfe alone, consistent with the idea that interaction between these two proteins contributes to the control of normal iron absorption. In addition to providing insight into the pathogenesis of HH, our results suggest that each of these genes might be a candidate modifier of the human hemochromatosis phenotype.

Animals↗
PubMed1997

Natural (Mg,Fe)SiO3-ilmenite and -perovskite in the Tenham meteorite.

The minerals (Mg,Fe)SiO3-ilmenite and -perovskite were identified in the shock-induced veins in the Tenham chondritic meteorite. Both phases are inferred to have transformed from pyroxene at high pressures and temperatures by shock metamorphism. Columnar-shaped ilmenite grains, one of two types of morphologies, have a topotaxial relationship with neighboring pyroxene grains, indicating shear transformation. Granular-shaped perovskite grains showed a diffraction pattern consistent with orthorhombic perovskite, but these grains were not stable under the electron beam irradiation and became amorphous. The higher iron concentration in both phases compared with those experimentally reported may suggest their metastable transition from enstatite because of shock compression.

Calcium Compounds↗
PubMed2006

Microbial studies of a selenium-contaminated mine site and potential for on-site remediation.

Surface water Selenium (Se) concentrations are above regulatory standards at several active and inactive phosphate mine sites in the US Western Phosphate Resource Area. The focus of the present study was to examine the impacts of the microbial communities on the oxidation state of Se in overburden waste from the Smoky Canyon phosphate mine in Idaho, USA. Microbial populations were found that reduce soluble selenate (SeO (4) (2-) ) to insoluble elemental Se. Microcosm experiments were conducted for molecular genetic analysis of this microbial community by rRNA gene profiling. An acetone pretreatment step was developed to remove interfering pre-petroleum hydrocarbons from the samples prior to extraction. PCR was used to amplify 16S and 18S rRNA genes present in the microbial community DNA. The amplified products were subjected to denaturing gradient gel electrophoresis (DGGE). Isolates and excised DGGE bands were amplified and sequenced for identification to determine the relative importance of culturable isolates to the total microbial population. Analysis of samples from different sites at the mine showed how Se contamination and previous remediation treatments changed the microbial populations across the site. Members of the family Enterobacteriaceae were dominant among the selenate reducing isolates from the site containing high Se levels. In particular, Serratia fonticola was isolated repeatedly from contaminated Smoky Canyon Mine site samples. Packed column studies were performed with seleniferous waste rock fractions from Smoky Canyon Mine. Column amendments consisted of combinations of iron, compost, and whey. Eh, pH, and extractable Se measurements were taken. Tests with infiltrated water showed columns containing an organic amendment combined with iron metal were the most resistant to Se leaching. Iron-based compounds from the corroding metal are thought to strongly bind the Se reduced by microbial activity, thereby stabilizing the Se in an insoluble form. We conclude that long-term stabilization of selenium at contaminated mine sites may require reductive microbial processes combined with abiotic immobilization by iron, either natural or engineered, to stabilize the Se and retard re-oxidation and release. Iron-selenide or iron-selenite compounds are more stable and resistant to leaching, especially when removed from active weathering.

Biodegradation, Environmental↗
PubMed1990

Citrate as a siderophore in Bradyrhizobium japonicum.

Under iron-limiting conditions, many bacteria secrete ferric iron-specific ligands, generically termed siderophores, to aid in the sequestering and transport of iron. One strain of the nitrogen-fixing soybean symbiont Bradyrhizobium japonicum, 61A152, was shown to produce a siderophore when 20 B. japonicum strains were screened with all six chemical assays commonly used to detect such production. Production by strain 61A152 was detected via the chrome azurol S assay, a general test for siderophores which is independent of siderophore structure. The iron-chelating compound was neither a catechol nor a hydroxamate and was ninhydrin negative. It was determined to be citric acid via a combination of thin-layer chromatography and high-voltage paper electrophoresis; this identification was verified by a specific enzymatic assay for citric acid. The inverse correlation which was observed between citric acid release and the iron content of the medium suggested that ferric citrate could serve as an iron source. This was confirmed via growth and transport assays. Exogenously added ferric citrate could be used to overcome iron starvation, and iron-deficient cells actively transported radiolabeled ferric citrate. These results, taken together, indicate a role for ferric citrate in the iron nutrition of this strain, which has been shown to be an efficient nitrogen-fixing strain on a variety of soybean cultivars.

Citrates↗
PubMed1990

Characterization of arsenopyrite oxidizing Thiobacillus. Tolerance to arsenite, arsenate, ferrous and ferric iron.

Two strains of Thiobacillus, T. ferrooxidans and T. thiooxidans, have been isolated from a bacterial inoculum cultivated during a one-year period in a 1001 continuous laboratory pilot for treatment of an arsenopyrite/pyrite concentrate. The optimum pH for the growth of both strains has been found to be between 1.7 and 2.5. Because of the high metal toxicity in bioleach pulps, the tolerance of T. ferrooxidans and T. thiooxidans with respect to iron and arsenic has been studied. The growth of both strains is inhibited with 10 g/l of ferric ion, 5 g/l of arsenite and 40 g/l of arsenate. 20 g/l of ferrous iron is toxic to T. ferrooxidans but 30 g/l is necessary to impede the growth of T. thiooxidans.

Acidithiobacillus thiooxidans↗
PubMed2004

Tolerance to stress and environmental adaptability of Chromobacterium violaceum.

Chromobacterium violaceum is a Gram-negative bacterium, abundant in a variety of ecosystems in tropical and subtropical regions, including the water and borders of the Negro River, a major component of the Amazon Basin. As a free-living microorganism, C. violaceum is exposed to a series of variable conditions, such as different sources and abundance of nutrients, changes in temperature and pH, toxic compounds and UV rays. These variations, and the wide range of environments, require great adaptability and strong protective systems. The complete genome sequencing of this bacterium has revealed an enormous number and variety of ORFs associated with alternative pathways for energy generation, transport-related proteins, signal transduction, cell motility, secretion, and secondary metabolism. Additionally, the limited availability of iron in most environments can be overcome by iron-chelating compounds, iron-storage proteins, and by several proteins related to iron metabolism in the C. violaceum genome. Osmotically inducible proteins, transmembrane water-channel, and other membrane porins may be regulating the movement of water and maintaining the cell turgor, activities which play an important role in the adaptation to variations in osmotic pressure. Several proteins related to tolerance against antimicrobial compounds, heavy metals, temperature, acid and UV light stresses, others that promote survival under starvation conditions, and enzymes capable of detoxifying reactive oxygen species were also detected in C. violaceum. All these features together help explain its remarkable competitiveness and ability to survive under different types of environmental stress.

Adaptation, Physiological↗
PubMed2005

Effect of the axial cysteine ligand on the electronic structure and reactivity of high-valent iron(IV) oxo-porphyrins (Compound I): a theoretical study.

The effect of axial ligands on the reactivity of high-valent iron(IV) oxo-porphyrins (Compound I) was investigated using the B3LYP hybrid density functional method. We studied alkane hydroxylation using four models: Compound I with thiolate, imidazole, phenolate, and chloride anions as axial ligands. The first three ligands were employed as models for cysteinate, histidine, and tyrosinate, respectively. Our calculations show that anionic ligands and neutral ligands favor different electronic states for stationary points in the reaction coordinate, and the calculated energy barrier and energy of several reaction intermediates show similar values. A remarkable effect of axial ligands was found in the final product release step. Our calculations show that the thiolate ligand weakens a bond between heme and an alcohol. In contrast, the imidazole ligand significantly increases the interaction between heme and an alcohol, which causes the catalytic cycle to be less efficient.

Computer Simulation↗
PubMed2003

Fate of uranyl in a quaternary system composed of uranyl, citrate, goethite, and Pseudomonas fluorescens.

This study investigated the partitioning of uranyl within a quaternary system made up of uranyl, citrate, goethite, and the bacterium Pseudomonas fluorescens. In the absence of cells, uranyl was sorbed to goethite as a complex involving surface groups and/or citrate. Measurements of the evolution of CO2 indicated that the addition of bacterial cells lead to the gradual biodegradation of citrate. Throughout the biodegradation process, uranyl remained sorbed to the insoluble fraction comprised of goethite and cells. EXAFS (Extended X-ray Absorption Fine Structure) measurements showed that bacterial cells outcompeted goethite for uranyl under the experimental conditions and caused the repartitioning of uranyl from goethite to cell matter, independently from citrate degradation. Citrate degradation caused further release of uranyl from goethite surfaces, followed by subsequent association of uranyl with cells. At long equilibration times (3 months), cell lysis and phosphate release resulted in the precipitation of an autunite-like phase. This work suggests that bacterial degradation of uranyl-complexing ligands in contaminated subsurface media containing iron oxides should not necessarily lead to an increase in the mobility of uranyl.

Biodegradation, Environmental↗
PubMed1983

Rapid resolution of transferrin C subtypes through isoelectric focusing with 2-mercaptoethanol.

The technique of choice currently used for the detection of serum transferrin molecular polymorphism is isoelectric focusing on polyacrylamide slab gels. However, this procedure is unsatisfactory for routine purposes, since a long pretreatment of the serum with iron-donor compounds or neuraminidase is necessary in order to obtain a complete resolution of the transferrin molecule. A very fast and highly economical standardized procedure for transferrin typing which enables a fair molecular resolution within only 3 1/2 h is reported. Protracted pretreatment of serum with neuraminidase or with iron-donor compounds can be totally avoided. An ultrathin layer of polyacrylamide gel is employed for the run, using pH ranges of 4-6.5 or 5-7. A short pretreatment of serum with a 13% solution of 2-mercaptoethanol is performed before the samples are placed on the gel. This technique has been used to perform transferrin typing in 396 cord serum samples from newborn infants of Arezzo (Tuscany), without occurrence of artifacts or the appearance of extra bands in transferrin patterns.

Humans↗
PubMed2003

[Octanhydroxamate of iron: synthesis, analysis and investigation of stability].

Hydroxamic acids are found as chelates in plants, as metabolites of bacteria and funges. Some aerobic microorganisms synthesize hydroxamic acids, which transmit iron from environment to the cells of the plants. Fourteen hydroxamic acids were synthesized and their interaction with iron (II and III) was investigated. The purpose of this investigation was synthesis of hydroxamic acids, creation of stable iron chelate with one of these acids, preparation of the methods of analysis, investigation of the stability of chelate and application for prophylaxis and treatment of iron deficiency anemia. We used octanhydroxamic acid for creation of chelate with iron. The synthesis of this acid was the cheapest and compound with iron appeared stable. Iron chelates after acid hydrolysis were analyzed by quantity of iron (9.8-12.3%). We used complexometric titration method with dinatrium salt of ethylendiamintetraacetic acid without indication for quantitative analysis. Iron (II) chelate is less stable, therefore, we used Fe (III) octanhydroxamate for further investigations. Preliminary trials with rabbits confirm rapid assimilation of iron (III) chelate from gastrointestinal tract and activation of erythropoiesis.

Anemia, Iron-Deficiency↗
PubMed1995

The hypotransferrinaemic mouse: ultrastructural and laser microprobe analysis observations.

Homozygote hypotransferrinaemic mice (hpx/hpx) have cytopathological features similar to those of human congenital atransferrinaemia, genetic haemochromatosis, and neonatal haemochromatosis. These conditions all have in common high levels of cytotoxic non-transferrin-bound serum iron. This study describes the ultrastructural features of iron overload in liver, pancreas, heart, and small intestine of 2- and 12-month-old hypotransferrinaemic mice. Electron microscopic studies of unstained sections showed early parenchymal cell siderosis, with accumulation of numerous ferritin particles and clusters in the cytosol, as well as ferritin and haemosiderin in lysosomes (siderosomes). In the 12-month-old animals, iron was also found in Kupffer cells and macrophages in other tissues. In addition, there were conspicuous iron-containing compounds in the bile canaliculi, and marked iron deposition in the pancreas and heart. Laser microprobe mass analysis (LAMMA) enabled localization and relative quantitation of iron deposition in subcellular compartments providing in situ documentation of iron accumulation in siderosomes and contributed in assessing total cytosolic iron in various cell types. Moreover, it demonstrated the importance and magnitude of the biliary route for iron excretion in these animals.

Animals↗
PubMed1988

Properties of N-hydroxy-N'-aminoguanidine derivatives as inhibitors of mammalian ribonucleotide reductase.

In previous studies, N-hydroxy-N'-aminoguanidine (HAG) derivatives were demonstrated to suppress growth and clonogenicity of tumor cells which correlated with the inhibition of ribonucleotide reductase and DNA synthesis. The present work has focused on the properties of five HAG derivatives as inhibitors of the ribonucleotide reductase from Ehrlich ascites tumor cells. HAG derivatives acted as non-competitive inhibitors of ribonucleotide reductase with respect to the substrates CDP and ADP. The apparent Ki values for the various HAG derivatives as inhibitors of CDP reductase ranged from 3.4 to 543 microM. However, the apparent Ki values for these inhibitors with respect to ADP reductase were 2- to 10-fold lower than the respective values for CDP reductase. After a preincubation of HAG derivatives and ribonucleotide reductase in the absence of substrates, an increased inhibition was observed. The activity of the inhibited enzyme could be restored by passage over a Sephadex G-25 column and subsequent incubation with dithioerythritol. The addition of either the non-heme iron subunit or the effector-binding subunit to the intact enzyme in the assay mixture resulted in a diminished inhibition of ADP reduction. Inhibition by HAG derivatives of ribonucleotide reductase activity in the test tube was not enhanced by iron chelators. However, a combination of HAG compounds and iron chelators synergistically inhibited the growth of L1210 cells.

Amines↗
PubMed1984

Mycobactins as chemotaxonomic characters for some rapidly growing mycobacteria.

Thirty-nine strains of rapidly growing mycobacteria were examined for the production of mycobactins (lipid-soluble, iron-binding compounds) when grown under conditions of iron-limitation on solidified medium. Different growth conditions had little effect on the structure of individual mycobactins, indicating them to be strongly conserved molecules showing intra-species consistency and thus suitable for use as chemotaxonomic characters of high discriminatory power. Strains of Mycobacterium aurum, M. chitae, M. chelonae subsp. abscessus, 'M. diernhoferi', M. duvalii, M. flavescens, M. fortuitum, M. gadium, 'M. gallinarum', M. neoaurum, M. parafortuitum, 'M. peregrinum', M. phlei, M. smegmatis, M. thermoresistible and M. vaccae formed mycobactins which were readily isolated and characterized by a combination of thin-layer and high-performance liquid chromatography. All strains of M. komossense and 'M. kanazawa' failed to produce a mycobactin; some strains of M. aurum, M. chelonae, M. parafortuitum, M. thermoresistible and M. vaccae were similarly negative. Mycobacteria of the M. fortuitum complex (M. fortuitum, M. chelonae and 'M. peregrinum') formed distinctive mycobactins, as did those in the M. parafortuitum complex (M. aurum, M. neoaurum, 'M. diernhoferi', M. vaccae and M. parafortuitum). The mycobactin from 'M. gallinarum' was different from those of the related species M. flavescens, for which four distinct mycobactin patterns were recorded. For routine examination of mycobactins in a diagnostic laboratory with limited resources, thin-layer chromatography used alone offers a simple but adequate means of characterization and final identification of the producing mycobacterium. High-performance liquid chromatography is only needed in those few instances where a high degree of discrimination is required.

Chromatography, High Pressure Liquid↗
PubMed1991

Iron sources for Haemophilus ducreyi.

The ability of various haem- and non-haem-iron-containing compounds to support the growth of iron-limited cultures of Haemophilus ducreyi was assessed in a plate bioassay. Only haemin or the haem-containing proteins, bovine haemoglobin, human haemoglobin and bovine catalase, but not equine cytochrome C111, were capable of serving as the sole exogenous iron source. Complexes of haptoglobin-haemoglobin and haem-serum albumin retained the ability to function as iron substrates. In contrast, no growth was observed with FeCl3, human lactoferrin and human transferrin. Siderophore production was not detected with a universal chemical assay. Outer-membrane-protein profiles derived from iron-starved cultures revealed four iron-regulated polypeptides of 65, 50, 45.5 and 40.5 Kda. These results indicate that haem can supply the requisite iron for growth of H. ducreyi.

Bacterial Outer Membrane Proteins↗
PubMed2005

Complexes of fulvic acid on the surface of hematite, goethite, and akaganeite: FTIR observation.

The present work extended our knowledge on the binding and complexation of a fulvic acid (FA) derived from leonardite and the iron oxides (hematite, goethite and akaganeite) by Fourier transform infrared spectroscopy (FTIR). As a prerequisite, the iron oxides were firstly prepared and characterized by transmission electron micrograph (TEM). All iron phases were single and well-described crystalloid. The FTIR data obtained by two different sampling preparation methods gave the consisting evidences that under our experimental conditions the interaction mechanism was to the ligand-exchange involving carboxylic functional groups of the FA and the surfaces sites of both hematite and goethite, while no complexation can be evidenced in the case of akaganeite, only surface adsorption. In general, the binding affinities of the iron oxides with the FA was in the order of hematite>goethite>akaganeite. The present method, although associated with some uncertainties, provided an opportunity to increase the knowledge in the field of the humic chemistry.

Benzopyrans↗