Ferritin—A general metal detoxicant

Binding of nonferrous metal ions to ferritin was compared to that of the phosphate-free or phosphate containing synthetic iron cores. The Scatchard plots for the synthetic cores reveal a high affinity site for Cd, Zn, Be, and Al, with K_D in the range 10^?5–10^?7 M. Preloading the cores with phosphate increased the number of metal ions bound without altering the K_D. The metal ions with smaller ionic radii (Be, Al) were bound in larger numbers than those with larger ionic radii (Cd, Zn). Ferritin isolated from soybean (Glycina max), horse spleen, and rat liver bound the metal ions in amounts larger than predicted from their iron core. Whereas the iron cores and their nonferrous metal ion complexes were insoluble, those in the protein shell remained in solution. Thus apoferritin precipitated with lower concentrations of aluminum than did holoferritin. Also, Al bound to apoferritin reduced the rate of iron loading into the protein.     

Metalloproteomics and metal toxicology of α-synuclein

Significant evidence has been accumulated linking exposure to heavy metals and/or distortion of metal homeostasis with the development of various neurodegenerative diseases. α-Synuclein is known to be involved in pathogenesis of a subset of neurodegenerative diseases collectively known as synucleinopathies. Therefore the interplay between metals, α-synuclein and neurodegeneration has attracted significant attention of researchers. This review discusses some of the aspects of the α-synuclein metalloproteomics and represents the peculiarities and consequences of α-synuclein interaction with various metal ions. Both non-specific and specific binding of this protein to metals is considered together with the analysis of the effects of such interactions on α-synuclein structure and aggregation propensity.     

Is chromium a trace essential metal?

If chromium is an essential metal it must have a specific role in an enzyme or cofactor, and a deficiency should produce a disease or impairment of function. To date, no chromium-containing glucose tolerance factor has been characterized, the purpose of the low-molecular-weight chromium-binding protein is questionable, and no direct interaction between chromium and insulin has been found. Furthermore, chromium3+ is treated like the toxic metals arsenic, cadmium, lead and mercury in animals. Chromium3+ may be involved in chromium6+-induced cancers because chromium6+ is converted to chromium3+ in vivo, and chromium3+ is genotoxic and mutagenic. Although there is no direct evidence of chromium deficiencies in humans, dietary supplements exist to provide supraphysiological doses of absorbable chromium3+. Chromium3+ may act clinically by interfering with iron absorption, decreasing the high iron stores that are linked to diabetes and heart disease. If so, this would make chromium3+ a pharmacological agent, not an essential metal.     

Phosphorylation-dependent metal binding by α-synuclein peptide fragments

α-Synuclein (α-syn) is the major protein component of the insoluble fibrils that make up Lewy bodies, the hallmark lesions of Parkinson’s disease. Its C-terminal region contains motifs of charged amino acids that potentially bind metal ions, as well as several identified phosphorylation sites. We have investigated the metal-binding properties of synthetic model peptides and phosphopeptides that correspond to residues 119–132 of the C-terminal, polyacidic stretch of human α-syn, with the sequence Ac-Asp-Pro-Asp-Asn-Glu-Ala-Tyr-Glu-Met-Pro-Ser-Glu-Glu-Gly (α-syn119–132). The peptide pY125 replaces tyrosine with phosphotyrosine, whereas pS129 replaces serine with phosphoserine. By using Tb³⁺ as a luminescent probe of metal binding, we find a marked selectivity of pY125 for Tb³⁺ compared with pS129 and α-syn119–132, a result confirmed by isothermal titration calorimetry. Truncated or alanine-substituted peptides show that the phosphoester group on tyrosine provides a metal-binding anchor that is supplemented by carboxylic acid groups at positions 119, 121, and 126 to establish a multidentate ligand, while two glutamic acid residues at positions 130 and 131 contribute to binding additional Tb³⁺ ions. The interaction of other metal ions was investigated by electrospray ionization mass spectrometry, which confirmed that pY125 is selective for trivalent metal ions over divalent metal ions, and revealed that Fe³⁺ and Al³⁺ induce peptide dimerization through metal ion cross-links. Circular dichroism showed that Fe³⁺ can induce a partially folded structure for pY125, whereas no change was observed for pS129 or the unphosphorylated analog. The results of this study show that the type and location of a phosphorylated amino acid influence a peptide’s metal-binding specificity and affinity as well as its overall conformation. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Chelation in metal intoxication—Principles and paradigms

The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The clinical use of the old chelators EDTA (ethylenediamine tetraacetate) and BAL (2,3-dimercaptopropanol) is now limited due to the inconvenience of parenteral administration, their own toxicity and tendency to increase the neurotoxicity of several metals. The hydrophilic dithiol chelators DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercapto-propanesulphonate) are less toxic and more efficient than BAL in the clinical treatment of heavy metal poisoning, and available as capsules for oral use. In copper overload, DMSA appears to be a potent antidote, although d-penicillamine is still widely used. In the chelation of iron, the thiols are inefficient, since iron has higher affinity for ligands with nitrogen and oxygen, but the new oral iron antidotes deferiprone and desferasirox have entered into the clinical arena. Comparisons of these agents and deferoxamine infusions are in progress. General principles for research and development of new chelators are briefly outlined in this review.     

Effect of nickel concentration and soil pH on metal accumulation and growth in tropical agromining ‘metal crops’

Plant and Soil - Phosphorus (P) deficiency is a major constraint for rice production in the tropics. Field-specific P management is key for resource-limited farmers to increase yields with minimal...     

Autophagy: a role in metal ion homeostasis?

Nutrient limitation is one of the most common forms of stress encountered by microorganisms in the environment. Surviving this stress depends upon a number of integrated responses, one of the most important of which is autophagy. When the filamentous fungus Aspergillus fumigatus becomes nutrient deprived it undergoes two important processes: the developmental pathway for asexual sporulation (conidiation), and a foraging response that promotes the migration of the hyphal tips into new substrate. To determine the contribution of autophagy to these two functions, we disrupted the A. fumigatus atg1 gene. The data reveal that Atg1 is required for wild-type conidiation of A. fumigatus, but only when nitrogen is limiting. Secondly, we demonstrate that metal ion availability limits the extent to which A. fumigatus can grow without a carbon/nitrogen source and that autophagy is necessary for growth under conditions of metal ion deficiency. These findings indicate that autophagy is responsible for maintaining an adequate supply of nitrogen to support conidiophore development, and provide intriguing new evidence that autophagy is linked to metal ion homeostasis.     

Metal–metal bonding in 1st, 2nd and 3rd row transition metal complexes: a topological analysis

A topological analysis based on density functional electronic and spin densities of the bonding characteristics in a series of Fe, Ru, Os, Tc and Rh dimers and trimers bridged, respectively, by μ-1,8-naphthyridine (nap) and μ-2,2′-dipyridylamine (dpa) is presented. By this simple qualitative analysis, we were able to determine the electronic ground state and correlated bonding order for a number of complexes potentially involved in extended metal atom chains (EMAC). Furthermore, we showed in the Ru dimer that it was possible to control the spin state simply by changing the bonded counter-anion.

Open image in new window

Graphical Abstract Electron localization analysis of the bonding properties in [M₂(nap)₄Cl₂]²⁺ and [M₃(dpa)₄(Cl₂] complexes

     

Do coinage metal anions interact with substituted benzene derivatives?

The nature of the anion–π interaction has been investigated by carrying out ab initio calculations of the complexes of coinage metal anions (Au^?, Ag^?, and Cu^?) with different kinds of π-systems. The binding energies indicate that gold anion has the highest and copper anion has the lowest affinity for interactions with π-systems. Different aspects of the anion–π interaction in these systems have been investigated, including charge-transfer effects (using the Merz–Kollman method), “atoms-in-molecules” (AIM) topological parameters, and interaction energies (using energy decomposition analysis, EDA). Our results indicated that, for most M^?···π interactions, the electrostatic term provides the dominant contribution, whereas polarization, charge transfer, and dispersion effects contribute less than 25 % of the interaction. We believe that the present results should lead to a greater understanding of the basis for anion–π interactions of coinage metal anions.     

Intestinal expression of metal transporters in Wilson’s disease

In Wilson’s disease (WND), biallelic ATP7B gene mutation is responsible for pathological copper accumulation in the liver, brain and other organs. It has been proposed that copper transporter 1 (CTR1) and the divalent metal transporter 1 (DMT1) translocate copper across the human intestinal epithelium, while Cu-ATPases: ATP7A and ATP7B serve as copper efflux pumps. In this study, we investigated the expression of CTR1, DMT1 and ATP7A in the intestines of both WND patients and healthy controls to examine whether any adaptive mechanisms to systemic copper overload function in the enterocytes. Duodenal biopsy samples were taken from 108 patients with Wilson’s disease and from 90 controls. CTR1, DMT1, ATP7A and ATP7B expression was assessed by polymerase chain reaction and Western blot. Duodenal CTR1 mRNA and protein expression was decreased in WND patients in comparison to control subjects, while ATP7A mRNA and protein production was increased. The variable expression of copper transporters may serve as a defense mechanism against systemic copper overload resulting from functional impairment of ATP7B.     

Free metal activity and total metal concentrations as indices of micronutrient availability to barley [Hordeum vulgare (L.) ‘Klages’]

The form in which a micronutrient is found in the rhizosphere affects its availability to plants. We compared the availability to barley of the free hydrated cation form of Fe³⁺, Cu²⁺, Zn²⁺, and Mn²⁺ versus their total metal concentrations (free ion plus complexes) in chelator-buffered solutions. Free metal ion activities were estimated using the chemical equilibrium program GEOCHEM-PC with the corrected database. In experiment 1, barley was grown in nutrient solutions with different Fe³⁺ activities using chelators to control Fe levels. Chlorosis occurred at Fe³⁺ activities of 10^–18 and 10^–19 M for barley grown in HEDTA and EDTA solutions, respectively. In experiment 2, barley was grown in nutrient solutions with the same calculated Fe³⁺ activity and the same chelator, but different total Fe concentrations. Leaf, root and shoot Fe concentrations were higher from CDTA buffered solutions which had the higher total Fe concentration indicating the importance of the total Fe concentration on Fe uptake. Results from treatments using EDTA or HEDTA, with one exception, were similar to the results from the CDTA treatment. This suggests differences in critical Fe³⁺ activities found in experiment 1 were due to differences in the total Fe concentration and not errors in chelate formation constants used to estimate the critical activities. Results for Cu, Zn, and Mn were similar to Fe; despite solutions with equal free Cu²⁺, Zn²⁺ and Mn²⁺ activities, plant concentrations of these metals were generally greater when grown in the solutions with the greater total amount of Cu, Zn, or Mn. When the free Zn²⁺ activity was kept constant while the total amount of Zn was increased from 4.4 to 49 M, leaf Zn concentration increased from 77 to 146 g g^-1. In order to predict metal availability to barley and other species in chelator-buffered nutrient solutions, both free and total metal concentrations in solution must be considered. The critical Fe³⁺ activities required by barley in this study are much higher than those from tomato and soybean, 10^-28 M, which strongly supports the Strategy 2 model of Fe uptake for Poaceae. This is related to the importance of the Fe³⁺ (barley) and the Fe²⁺ (tomato and soybean) ions in Fe uptake. Fe-stressed barley is known to release phytosiderophores which compete for Fe³⁺ in the nutrient solution, while tomato and soybean reduce Fe³⁺ to Fe²⁺ at the epidermal cell membranes to allow uptake of Fe²⁺ from Fe³⁺ chelates in solution.Abbreviations CDTA trans-1,2-diaminocyclohexane-N,N,N,N-tetracetic acid - DTPA diethylenetriaminepentacetic acid - EDTA ethylenediaminetetracetic acid - EDDHA ethylenediamine-di(o-hydroxyphenylacetic acid) - HBED-N,N di(2-hydroxybenzoyl)-ethylenediamine-N,N-diacetic acid - HEDTA-N hydroxyethylenediaminetriacetic acid - MES-2 (N-morpholino)ethanesulfonic acid - NTA nitrilotriacetic acid     

Cooperative adsorption of critical metal ions using archaeal poly-γ-glutamate

Antimony, beryllium, chromium, cobalt (Co), gallium (Ga), germanium, indium (In), lithium, niobium, tantalum, the platinoids, the rare-earth elements (including dysprosium, Dy), and tungsten are generally regarded to be critical (rare) metals, and the ions of some of these metals are stabilized in acidic solutions. We examined the adsorption capacities of three water-soluble functional polymers, namely archaeal poly-γ-glutamate (L-PGA), polyacrylate (PAC), and polyvinyl alcohol (PVA), for six valuable metal ions (Co²⁺, Ni²⁺, Mn²⁺, Ga³⁺, In³⁺, and Dy³⁺). All three polymers showed apparently little or no capacity for divalent cations, whereas L-PGA and PAC showed the potential to adsorb trivalent cations, implying the beneficial valence-dependent selectivity of anionic polyelectrolytes with multiple carboxylates for metal ions. PVA did not adsorb metal ions, indicating that the crucial role played by carboxyl groups in the adsorption of crucial metal ions cannot be replaced by hydroxyl groups under the conditions. In addition, equilibrium studies using the non-ideal competitive adsorption model indicated that the potential for L-PGA to be used for the removal (or collection) of water-soluble critical metal ions (e.g., Ga³⁺, In³⁺, and Dy³⁺) was far superior to that of any other industrially-versatile PAC materials.     

Ulltrastructural and trace metal studies on radiographers’ hair and nails

Scalp hair and fingernail samples of 42 medical radiographers and 42 nonradiographers (control) with matching age groups and food habits were collected for this study. Trace metal estimation by atomic absorption spectrometry (AAS) has indicated a significant increase (P < 0.001) in Zn, Cu, and Cd contents in the radiographers’ hair and nails. Scanning electron microscopy (SEM) reveled structural changes in the hair and nails of radiographers. Significant alterations in the Zn and Cd contents along with extensive structural damage in the hair and nails probably indicate that low-dose Χ-radiation imposes stress on these radiation workers.     

Simplified heavy metal staining techniques demonstrated with Fast Plant leaf tissue

Fast Plant (Brassica rapa,Cruciferae)leaf tissue fixed in glutaradehyde-acrolein and post-fixed in osmium,was examined for response to several easilyprepared heavy metal stains.Lead and uranium,separately and in combination,gave typical results across the spectrum of cell orgeanelles.As s single stain following osmium,bismuth produced images seemingly equivalent to lead and uranium.Phosphotungstic acid produced very good membrane delineation but produced a washed-out background image similar to that from lead staining .Carbohydrate compounds were especially responsive to ruthenium;the cytoplasm and the matrix of all organelles were also stained very well.The procedures were no more demanding than traditional staining methods and may be easily used in research and teaching .Fast Plant materials are a reliable,quick nand easy source of living material.     

Simplified heavy metal staining techniques demonstrated with Fast Plant leaf tissue

Fast Plant(Brassica rapa,Cruciferae)leaf tissuefixed in glutaraldehyde-acrolein and post-fixed in os-mium,was examined for response to several easily-prepared heavy metal stains.Lead and uranium,separately and in combination,gave typical resultsacross the spectrum of cell organellets.As a single stainfollowing osmium,bismuth produced images seeminglyequivalent to lead and uranium.Phosphotungstic acidproduced very good membrane delineation but produceda washed-out background image similar to that from leadstaining.Carbohydrate compounds were especiallyresponsive to ruthenium;the cytoplasm and the matrixof all organelles were also stained very well.Theprocedures were no more demanding than traditionalstaining methods and may be easily used in research andteaching.Fast Plant materials are a reliable,quick andeasy source of living material.     

Simultaneous sewage sludge digestion and metal leaching — effect of temperature

The effect of temperature on the simultaneous sewage sludge digestion and metal leaching process was studied in laboratory bioreactors of 20 l working volume. The results thus obtained showed that the process can be employed efficiently for metal solubilization, elimination of indicator microorganisms and sewage sludge stabilization at temperatures between 10°C and 30°C. Rates of pH reduction, sulfur oxidation, growth of thiobacilli, elimination of indicator microorganisms and solids degradation were found to decrease with temperature. Low metal solubilization efficiency was observed at 10°C; however, metals were solubilized to below the recommended level. The solubilization of organic matter and nutritive elements (N, P and K) was not significantly affected by the variation in temperature. The fertilizer value of sludge after leaching and digestion did not change significantly and remained the same irrespective of temperature. *** DIRECT SUPPORT *** AG903078 00005     

Molecular simulations in metal–organic frameworks for diverse potential applications

As a new class of intriguing nanoporous materials, metal–organic frameworks (MOFs) have been considered for diverse potential applications. The number of MOFs synthesised to date is extremely large; thus, experimental testing alone is economically expensive and practically formidable. With rapidly growing computational resources, molecular simulation has become an indispensable tool to characterise, screen and design MOFs. Our research group has conducted comprehensive simulation studies in MOFs for carbon capture, hydrocarbon separation, alcohol adsorption and biofuel purification, water treatment, bio- and chiral separation and drug loading; furthermore, mechanical moduli, structural transition and thermal conductivity have also been examined. These systematic simulation studies are summarised in this review to demonstrate that simulation at a molecular level can secure the quantitative interpretation of experimental observation, provide the microscopic insight from bottom-up and facilitate the development of new MOFs.     

Kinetics and equilibria of metal‐containing materials: Ramifications for aquatic toxicity testing for classification of sparingly soluble metals,inorganic metal compounds and minerals

The concentration of soluble metal more closely reflects the bioavailable fraction than does the total or “nominal”; concentration which includes the undissolved portion of the compound being tested. Consideration of metal species would provide a better estimation of bioavailability of the metal. Because the solubility of sparingly soluble metals, metal compounds and minerals depends on the dissolution conditions, aquatic toxicity tests may produce different results depending on the protocol used for the preparation of the test solutions. This paper considers critical aspects of the physical and chemical processes associated with dissolution. The kinetics and equilibria associated with the dissolution of sparingly soluble metals, metal compounds and minerals are reviewed, with special reference to the influence of grinding of materials. This is of importance in the regulatory classification of sparingly soluble compounds. A protocol that is appropriate for preparation of solutions for aquatic toxicity testing of sparingly soluble metals, metal compounds and minerals is recommended. The appropriateness of the results obtained using the proposed protocol for determining environmental risk is carefully considered, and the importance of considering both the actual concentrations of metal that would be in the environment and the bioavailability of the metal species present is highlighted.