Eliminating Competition: Characterizing and Eliminating Competitive Binding at Separate Sites between DAHP Synthase’s Essential Metal Ion and the Inhibitor DAHP Oxime

Biochemistry ◽  
2018 ◽  
Vol 57 (48) ◽  
pp. 6679-6687 ◽  
Author(s):  
Maren Heimhalt ◽  
Shan Jiang ◽  
Paul J. Berti
Keyword(s):  
Metal Ion ◽  
Competitive Binding ◽  
Essential Metal

scholarly journals Gestational Cd Exposure in the CD-1 Mouse Sex-Specifically Disrupts Essential Metal Ion Homeostasis

2021 ◽  
Author(s):  
Thomas W Jackson ◽  
Oliver Baars ◽  
Scott M Belcher
Keyword(s):  
Metal Ion ◽  
Ion Homeostasis ◽  
Female Offspring ◽  
Hepatic Insulin Resistance ◽  
Liver Iron ◽  
Metal Concentrations ◽  
Essential Metal ◽  
Metal Ion Homeostasis ◽  
Placental Efficiency ◽  
Metabolic Disruption

In CD-1 mice, gestational-only exposure to cadmium (Cd) causes female-specific hepatic insulin resistance, metabolic disruption, and obesity. To evaluate whether sex differences in cadmium uptake and changes in essential metal concentrations contribute to metabolic outcomes, placental and liver cadmium and essential metal concentrations were quantified in male and female offspring perinatally exposed to 500 ppb CdCl2. Exposure resulted in increased maternal liver Cd+2 concentrations (364 microgram/kg) similar to concentrations found in non-occupationally exposed human liver. At gestational day (GD) 18, placental cadmium and manganese concentrations were significantly increased in exposed males and females, and zinc was significantly decreased in females. Placental efficiency was significantly decreased in GD18 exposed males. Increases in hepatic Cd concentrations and a transient prenatal increase in zinc were observed in exposed female liver. Fetal and adult liver iron concentrations were decreased in both sexes, and decreases in hepatic zinc, iron, and manganese were observed in exposed females. Analysis of GD18 placental and liver metallothionein mRNA expression revealed significant Cd-induced upregulation of placental metallothionein in both sexes, and a significant decrease in fetal hepatic metallothionein in exposed females. In placenta, expression of metal ion transporters responsible for metal ion uptake was increased in exposed females. In liver of exposed adult female offspring, expression of the divalent cation importer (Slc39a14/Zip14) decreased, whereas expression of the primary exporter (Slc30a10) increased. These findings demonstrate that Cd can preferentially cross the female placenta, accumulate in the liver, and cause lifelong dysregulation of metal ion concentrations associated with metabolic disruption.

Comparative Study of Thyroxine Assays Employing Kit Radio-Ligand Reagents

1973 ◽  
Vol 10 (1-6) ◽  
pp. 14-22 ◽  
Author(s):  
D. Watson ◽  
S. Lees
Keyword(s):  
Comparative Study ◽  
Protein Binding ◽  
Metal Ion ◽  
Competitive Binding ◽  
Competitive Protein Binding

A comparative study of some ‘kit’ radiometric procedures for the determination of thyroxine in serum is reported. Four manufacturers' competitive-binding reagents and methods—three incorporating prior extraction and one employing column elution—are examined. Considerable discrepancies exist between the manufacturers' ‘standards’ which, in the main, account for the differences in results obtained by the different methods. Other deficiencies include susceptibility to metal ion interference, variation (up to 8%) in thyroxine extraction and non-specific, i.e. ‘mimic T-4’, measurement. Radio-ligand reagent ‘kits’ need to be critically assessed before being used routinely. Separation of hypo-and hyperthyroid from euthyroid patients is achieved as well with some competitive protein-binding T-4 methods as with serum PBI.

scholarly journals Naphthoquinone based chemosensors for transition metal ions: experiment and theory

RSC Advances ◽  
2017 ◽  
Vol 7 (87) ◽  
pp. 55163-55174 ◽  
Author(s):  
Prajkta Gosavi-Mirkute ◽  
Amit Patil ◽  
Dipali N. Lande ◽  
Debamitra Chakravarty ◽  
Shridhar P. Gejji ◽  
...  
Keyword(s):  
Transition Metal ◽  
Metal Ions ◽  
Metal Ion ◽  
Ph Effect ◽  
Transition Metal Ions ◽  
Competitive Binding ◽  
Ion Binding ◽  
Solvent Mixtures ◽  
Metal Ion Binding

Naphthoquinone based chemosensors are studied for metal ion binding in methanol–water–triethylamine solvent mixtures. pH effect, M : L stoichiometry and competitive binding of metal ions is studied.

RNAs' uracil quartet model with a non-essential metal ion

2011 ◽  
Vol 47 (16) ◽  
pp. 4646 ◽  
Author(s):  
Miquel Barceló-Oliver ◽  
Carolina Estarellas ◽  
Àngel Terrón ◽  
Ángel García-Raso ◽  
Antonio Frontera
Keyword(s):  
Metal Ion ◽  
Essential Metal

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 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.

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