scholarly journals Homoeostasis and distribution of essential metals in cells: Principles and molecular mechanisms

2012 ◽  
Vol 34 (5) ◽  
pp. 4-13 ◽  
Author(s):  
Claudia Blindauer
Keyword(s):  
Metal Ions ◽  
Metal Ion ◽  
Molecular Mechanisms ◽  
Genetic Diseases ◽  
Pernicious Anaemia ◽  
Acrodermatitis Enteropathica ◽  
Essential Metals ◽  
Essential Metal ◽  
Parkinson’S Diseases ◽  
Multicellular Organisms

It has long been recognized that all organisms have a requirement for a range of metal ions, serving a variety of purposes (Table 1)1. The consequences of deficiency for each of these metal ions are grave; however, even essential metal ions are demonstrably toxic at elevated concentrations2. Therefore both unicellular and multicellular organisms have developed sophisticated mechanisms to regulate the intracellular concentrations and distribution of essential metal ions. The importance of such mechanisms is illustrated by the severity of genetic diseases related to metal mishandling, which include thalassaemias (iron overload), pernicious anaemia (diminished cobalt absorption), Wilson's and Menkes' diseases (copper mis-distribution), and acrodermatitis enteropathica (congenital zinc deficiency)3, with several of these diseases being fatal if untreated. It is also thought that impaired metal ion homoeostasis is a hallmark of aging4, and several neurodegenerative diseases including Alzheimer's and Parkinson's diseases are also intimately linked to misbalanced metal distribution5.

scholarly journals An Appraisal of the Field of Metallomics and the Roles of Metal Ions in Biochemistry and Cell Signaling

2021 ◽  
Vol 11 (22) ◽  
pp. 10846
Author(s):  
Wolfgang Maret
Keyword(s):  
Applied Sciences ◽  
Metal Ions ◽  
Evolutionary History ◽  
Chemical Elements ◽  
Building Blocks ◽  
Living Cells ◽  
Manufacturing Processes ◽  
Essential Metals ◽  
Essential Metal ◽  
Functional Consequences

Humans require about 20 chemical elements. Half of them are essential metal ions. Many additional, non-essential metal ions are present in our bodies through environmental exposures, including in our diet, with functional consequences. Their accumulation is accelerated due to the increasing pollution of soil, air, water and manufacturing processes that employ chemical elements to which we have not been exposed in our evolutionary history. Yet other metal ions are essential for other forms of life, which calls on life scientists to consider the interactions of life processes with most of the chemical elements in the periodic table. Only in this century have attempts been made to integrate specialty disciplines into a science of bioelements called metallomics. Metallomics forms a fifth group when added to the traditional four building blocks of living cells and their areas of investigations, i.e., sugars (glycomics), fats (lipidomics), proteins (proteomics) and nucleic acids (genomics). Neither an understanding of all the essential metals and their interactions nor the functional impacts of the non-essential metals for life, except established toxic elements such as lead, are widely perceived as important in the basic science communities and in the applied sciences such as medicine and engineering. It is a remarkable oversight that this article attempts to address with representative examples.

The role of metal ions in the virulence and viability of bacterial pathogens

2019 ◽  
Vol 47 (1) ◽  
pp. 77-87 ◽  
Author(s):  
Stephanie L. Begg
Keyword(s):  
Metal Ions ◽  
Metal Ion ◽  
Molecular Mechanisms ◽  
Bacterial Pathogens ◽  
Ion Homeostasis ◽  
Transition Metal Ions ◽  
Metal Ion Homeostasis ◽  
And Function ◽  
Iron Manganese

AbstractMetal ions fulfil a plethora of essential roles within bacterial pathogens. In addition to acting as necessary cofactors for cellular proteins, making them indispensable for both protein structure and function, they also fulfil roles in signalling and regulation of virulence. Consequently, the maintenance of cellular metal ion homeostasis is crucial for bacterial viability and pathogenicity. It is therefore unsurprising that components of the immune response target and exploit both the essentiality of metal ions and their potential toxicity toward invading bacteria. This review provides a brief overview of the transition metal ions iron, manganese, copper and zinc during infection. These essential metal ions are discussed in the context of host modulation of bioavailability, bacterial acquisition and efflux, metal-regulated virulence factor expression and the molecular mechanisms that contribute to loss of viability and/or virulence during host-imposed metal stress.

scholarly journals Alkali-metal-ion- and H+-dependent activation and/or inhibition of intestinal brush-border sucrase. A model involving three functionally distinct key prototropic groups

1988 ◽  
Vol 251 (3) ◽  
pp. 667-675 ◽  
Author(s):  
M Vasseur ◽  
G Van Melle ◽  
R Frangne ◽  
F Alvarado
Keyword(s):  
Alkali Metal ◽  
Metal Ions ◽  
Brush Border ◽  
Metal Ion ◽  
Molecular Mechanisms ◽  
Competitive Inhibitor ◽  
Ionization Constants ◽  
Alkali Metal Ions ◽  
Alkali Metal Ion ◽  
Intestinal Brush Border

For rabbit intestinal brush-border sucrase, a model based on classical Michaelis-Dixon theory cannot fully explain the peculiar antagonistic relationship existing between the substrate and one key proton, Hx, which at acid pH values behaves as a fully competitive inhibitor. In the same pH range, a second proton, Hy, is responsible for changes in catalytic activity and behaves as a mixed-type partially non-competitive inhibitor [Vasseur, Tellier & Alvarado (1982) Arch. Biochem. Biophys. 218, 263-274]. Although involved in the same ionization reaction, these two protons have different kinetic functions, since they are responsible for affinity-type and capacity-type effects respectively. Depending on whether Hx is bound or not, we postulate the enzyme to alternate between two distinct forms differing in their binding properties. The alkali-metal ions Na+ and Li+ have a concentration-dependent biphasic effect on this equilibrium. At low concentrations they facilitate the release of Hx, resulting in K-type activation. At higher concentrations they favour enzyme reprotonation, causing K-type inhibition. On the basic side of the pH spectrum, our results confirm the existence of separate non-competitive effects of the alkali-metal ions, particularly Li+ [Alvarado & Mahmood (1979) J. Biol. Chem. 254, 9534-9541]. To explain the molecular mechanisms underlying the alkali-metal-ion- and H+-dependent effects, we formulate a sucrase model, the three-protons model, in which the acid and basic ionization constants involve respectively two and one key prototropic groups that are functionally distinguishable. A global iterative fit of the relevant general equation to our whole set of data has permitted us to estimate the numerical value of each of the constants constituting the model.

scholarly journals Physical Interaction and Functional Coupling between ACDP4 and the Intracellular Ion Chaperone COX11, an Implication of the Role of ACDP4 in Essential Metal Ion Transport and Homeostasis

2005 ◽  
Vol 1 ◽  
pp. 1744-8069-1-15 ◽  
Author(s):  
Dehuang Guo ◽  
Jennifer Ling ◽  
Mong-Heng Wang ◽  
Jin-Xiong She ◽  
Jianguo Gu ◽  
...  
Keyword(s):  
Metal Ions ◽  
Metal Ion ◽  
Spinal Cord Dorsal Horn ◽  
Hek293 Cells ◽  
Functional Coupling ◽  
Essential Metal ◽  
Dorsal Horn Neurons ◽  
Copper Manganese ◽  
Spinal Cord Dorsal

Divalent metal ions such as copper, manganese, and cobalt are essential for cell development, differentiation, function and survival. These essential metal ions are delivered into intracellular domains as cofactors for enzymes involved in neuropeptide and neurotransmitter synthesis, superoxide metabolism, and other biological functions in a target specific fashion. Altering the homeostasis of these essential metal ions is known to connect to a number of human diseases including Alzheimer disease, amyotrophic lateral sclerosis, and pain. It remains unclear how these essential metal ions are delivered to intracellular targets in mammalian cells. Here we report that rat spinal cord dorsal horn neurons express ACDP4, a member of Ancient Conserved Domain Protein family. By screening a pretransformed human fetal brain cDNA library in a yeast two-hybrid system, we have identified that ACDP4 specifically interacts with COX11, an intracellular metal ion chaperone. Ectopic expression of ACDP4 in HEK293 cells resulted in enhanced toxicity to metal ions including copper, manganese, and cobalt. The metal ion toxicity became more pronounced when ACDP4 and COX11 were co-expressed ectopically in HEK293 cells, suggesting a functional coupling between them. Our results indicate a role of ACDP4 in metal ion homeostasis and toxicity. This is the first report revealing a functional aspect of this ancient conserved domain protein family. We propose that ACDP is a family of transporter protein or chaperone proteins for delivering essential metal ions in different mammalian tissues. The expression of ACDP4 on spinal cord dorsal horn neurons may have implications in sensory neuron functions under physiological and pathological conditions.

scholarly journals The Mechanism of Metal Homeostasis in Plants: A New View on the Synergistic Regulation Pathway of Membrane Proteins, Lipids and Metal Ions

Membranes ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 984
Author(s):  
Danxia Wu ◽  
Muhammad Saleem ◽  
Tengbing He ◽  
Guandi He
Keyword(s):  
Membrane Proteins ◽  
Metal Ions ◽  
Metal Ion ◽  
Molecular Mechanisms ◽  
Lipid Membrane ◽  
Plant Cells ◽  
Metal Homeostasis ◽  
Mitogen Activated Protein Kinase ◽  
Specific Substrate ◽  
Plant Tolerance

Heavy metal stress (HMS) is one of the most destructive abiotic stresses which seriously affects the growth and development of plants. Recent studies have shown significant progress in understanding the molecular mechanisms underlying plant tolerance to HMS. In general, three core signals are involved in plants’ responses to HMS; these are mitogen-activated protein kinase (MAPK), calcium, and hormonal (abscisic acid) signals. In addition to these signal components, other regulatory factors, such as microRNAs and membrane proteins, also play an important role in regulating HMS responses in plants. Membrane proteins interact with the highly complex and heterogeneous lipids in the plant cell environment. The function of membrane proteins is affected by the interactions between lipids and lipid-membrane proteins. Our review findings also indicate the possibility of membrane protein-lipid-metal ion interactions in regulating metal homeostasis in plant cells. In this review, we investigated the role of membrane proteins with specific substrate recognition in regulating cell metal homeostasis. The understanding of the possible interaction networks and upstream and downstream pathways is developed. In addition, possible interactions between membrane proteins, metal ions, and lipids are discussed to provide new ideas for studying metal homeostasis in plant cells.

Peptide models in the study of the mechanism of carcinogenesis by heavy metals

2011 ◽  
Vol 83 (9) ◽  
pp. 1751-1762 ◽  
Author(s):  
Gerasimos Malandrinos ◽  
Ana-Monica Nunes ◽  
Kimon Zavitsanos ◽  
Nick Hadjiliadis
Keyword(s):  
Metal Ions ◽  
Metal Ion ◽  
Molecular Mechanisms ◽  
Peptide Fragments ◽  
Metal Ion Binding ◽  
Peptide Models ◽  
Strand Breakage ◽  
Mechanisms Of Carcinogenesis ◽  
Dna Strand ◽  
Almost All

The molecular mechanisms of carcinogenesis involving heavy metal ions are not yet fully understood. Histones surrounding DNA are believed to be primary targets for metal ion binding, and such interactions may play a direct or indirect role in metal-induced toxicity carcinogenesis. This paper reviews our results of approximately the last 10 years in this area, starting from small peptide fragments and models of various histones and ending with longer ones. It was found that almost all peptide models reacted strongly with metal ions, and in some cases the peptides in the presense of Cu(II) or Ni(II) were hydrolyzed. Oxidation of deoxyguanosine to 8-oxo-deoxyguanosine under physiological pH values was also observed in the presense of mild oxidation agents like H2O2 and certain metal ion–peptide complexes. With longer peptide chain models, a DNA strand breakage analysis was also carried out, indicating an increased DNA damage by Cu2+/H2O2 and Ni2+/H2O2 reaction mixtures. The results lead to proposals of possible mechanistic pathways of carcinogenesis caused by Cu(II) and Ni(II).

New sulfonamide complexes with essential metal ions [Cu (II), Co (II), Ni (II) and Zn (II)]. Effect of the geometry and the metal ion on DNA binding and nuclease activity. BSA protein interaction

2020 ◽  
Vol 202 ◽  
pp. 110823 ◽  
Author(s):  
Tamara Tŏpala ◽  
Alejandro Pascual–Álvarez ◽  
M. Ángeles Moldes–Tolosa ◽  
Andreea Bodoki ◽  
Alfonso Castiñeiras ◽  
...  
Keyword(s):  
Dna Binding ◽  
Metal Ions ◽  
Protein Interaction ◽  
Metal Ion ◽  
Nuclease Activity ◽  
Essential Metal

Metal Toxicity and Speciation: A Review

2021 ◽  
Vol 28 ◽  
Author(s):  
Massimiliano Peana ◽  
Alessio Pelucelli ◽  
Serenella Medici ◽  
Rosita Cappai ◽  
Valeria Marina Nurchi ◽  
...  
Keyword(s):  
Metal Ions ◽  
Toxic Metals ◽  
Toxic Metal ◽  
Cellular Damage ◽  
Anthropogenic Sources ◽  
Essential Metals ◽  
Essential Metal ◽  
Toxic Metal Ions ◽  
Cellular Targets ◽  
Hard Structures

Background : Essential metal ions play a specific and fundamental role in human metabolism. Their homeostasis is finely tuned and any concentration imbalance in form of deficiency or excess could lead to a progressive reduction and failure of normal biological function, to severe physiological and clinical outcomes till death. Conversely, non-essential metals are not necessary for life and only noxious effects could arise after their exposure. Large environmental amounts of such chemicals come from both natural and anthropogenic sources, with the latter being predominant because of human activities. The dissipation of toxic metals contaminates water, air, soil, and food, causing a series of chronic and acute syndromes. Objective : This review discusses the toxicity of non-essential metals considering their peculiar chemical characteristics such as different forms, hard-soft character, oxidation states, binding capabilities and solubility, which can influence their speciation in biological systems, and subsequently, the main cellular targets. Particular focus is given to selected toxic metals, major non-essential metals or semimetals related to toxicity such as mercury, lead, cadmium, chromium, nickel and arsenic. In addition, we provide indications on the possible treatments/interventions on metal poisoning based on chelation therapy. Conclusion: Toxic metal ions can exert their peculiar harmful effects in several ways. They strongly coordinate to important biological molecules on the basis of their chemical-physical characteristics (manly HSAB properties) or replace essential metal ions from their natural locations in proteins, enzymes or in hard structures such as bones or teeth. Metals with redox properties could be key inducers of reactive oxygen species, leading to oxidative stress and cellular damage. Therapeutic detoxification, through complexation of toxic metal ions by specific chelating agents, appears an efficacious clinical strategy mainly in acute cases of metal intoxication.

Use of agro-waste (Musa paradisiaca peels) as a sustainable biosorbent for toxic metal ions removal from contaminated water

2019 ◽  
Author(s):  
Chem Int
Keyword(s):  
Heavy Metal ◽  
Metal Ions ◽  
Contact Time ◽  
Metal Ion ◽  
Equilibrium Concentration ◽  
Ion Concentration ◽  
Contaminated Water ◽  
Musa Paradisiaca ◽  
Percentage Removal ◽  
Adsorbent Dose

A study of removal of heavy metal ions from heavy metal contaminated water using agro-waste was carried out with Musa paradisiaca peels as test adsorbent. The study was carried by adding known quantities of lead (II) ions and cadmium (II) ions each and respectively into specific volume of water and adding specific dose of the test adsorbent into the heavy metal ion solution, and the mixture was agitated for a specific period of time and then the concentration of the metal ion remaining in the solution was determined with Perkin Elmer Atomic absorption spectrophotometer model 2380. The effect of contact time, initial adsorbate concentration, adsorbent dose, pH and temperature were considered. From the effect of contact time results equilibrium concentration was established at 60minutes. The percentage removal of these metal ions studied, were all above 90%. Adsorption and percentage removal of Pb2+ and Cd2+ from their aqueous solutions were affected by change in initial metal ion concentration, adsorbent dose pH and temperature. Adsorption isotherm studies confirmed the adsorption of the metal ions on the test adsorbent with good mathematical fits into Langmuir and Freundlich adsorption isotherms. Regression correlation (R2) values of the isotherm plots are all positive (>0.9), which suggests too, that the adsorption fitted into the isotherms considered.

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