Cellular Metal-ion Homeostasis

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What is the primary reason for metal-ion toxicity in cells?

Impaired passive transport through the cell membrane

Disruption of metal-regulated transcription and translation

Changes in pH and redox state

Binding to inappropriate sites and subsequent reaction chemistry (correct)

What is the purpose of maintaining metal-ion concentrations within certain ranges in cells?

To facilitate energy storage and transmission

To modulate ion channel and pump activity

To control protein structural changes

To regulate metal-ion deficiency and toxicity (correct)

How do cells achieve metal-ion homeostasis and detoxification?

By employing a variety of mechanisms, including extracellular metal carriers and metal-mediated protein structural changes (correct)

Through changes in pH and redox state

Through the action of ion channels and pumps

By using metal-regulated transcription and translation

What happens when the concentration of an essential metal ion is too low?

Processes that need to use that ion will be adversely affected Signup and view all the answers

What is the consequence of increasing the concentration of a metal ion beyond an upper threshold?

The effects of metal-ion toxicity will arise Signup and view all the answers

What is the purpose of zon-concentration gradients in cells?

To store and transmit energy and information Signup and view all the answers

What happens when a metal ion binds at an inappropriate site?

It competes with other beneficial metal ions for that site. Signup and view all the answers

What is the term for the maintenance of the concentration of beneficial metal ions in the correct range?

Homeostasis Signup and view all the answers

What can be a consequence of metal ions binding nonspecifically to certain sites?

Inhibition of normal biological processes Signup and view all the answers

Why can excess iron be toxic?

It can catalyze the formation of oxygen-based free radicals Signup and view all the answers

What is the purpose of giving desferrioxamine to patients with iron overload?

To chelate iron and facilitate its excretion Signup and view all the answers

What is a characteristic of platinum(I1) complexes?

They are rather inert to substitution Signup and view all the answers

What is the result of the substitution reactions of chloride ions with cisplatin?

The formation of stable adducts with DNA Signup and view all the answers

Why is cis-[Pd(NH3)2Cl2] not used in cancer chemotherapy?

It is too toxic to be used Signup and view all the answers

What is a consequence of metal ions not utilized in biological systems?

They can be toxic Signup and view all the answers

What is the term for the removal of toxic concentrations of nonbeneficial metal ions?

Detoxification Signup and view all the answers

What is the result of protonation of the carbonate and tyrosinate ligands in the endosome?

Release of iron Signup and view all the answers

What is the role of clathrin in receptor-mediated endocytosis?

It promotes the formation of a coated vesicle Signup and view all the answers

What is the function of ferritin?

To store iron for later use Signup and view all the answers

How does the Fur protein regulate gene expression in bacteria?

By binding to specific DNA sequences in the presence of divalent metal ions Signup and view all the answers

What is the purpose of the ATP-driven proton pumps in the endosome?

To lower the pH in the endosome Signup and view all the answers

What is the role of the transferrin receptor?

To facilitate the uptake of iron into the cell Signup and view all the answers

What happens to the vesicle containing the receptor with apotransferrin bound after it fuses with the plasma membrane?

The apotransferrin is released Signup and view all the answers

How is the expression of ferritin regulated in mammals?

At the translational level Signup and view all the answers

What is the function of the coated pit in receptor-mediated endocytosis?

To facilitate the formation of a coated vesicle Signup and view all the answers

What is the role of pH in the regulation of iron uptake and storage?

It regulates the release of iron from the transferrin Signup and view all the answers

What is the main challenge in regulating iron levels in organisms?

Iron(II) is quite insoluble at neutral pH Signup and view all the answers

What is the role of transferrin proteins in iron transport?

To solubilize and transport iron throughout the body Signup and view all the answers

What is the synergistic effect of carbonate binding to transferrin proteins?

It facilitates iron release within cells Signup and view all the answers

What is the structure of transferrin proteins?

Two similar domains, each of which binds one iron atom Signup and view all the answers

What is the coordination sphere of the iron atom in transferrin proteins?

A distorted octahedral sphere with two phenolate oxygens, one imidazole nitrogen, one carboxylate oxygen, and two oxygens from the bound carbonate Signup and view all the answers

What is the role of siderophores in iron transport?

To sequester and facilitate iron transport into bacterial cells Signup and view all the answers

What is the apparent binding constant of transferrin proteins for Fe(II) ions?

10^5 M-1 Signup and view all the answers

What is the effect of iron binding on the structure of transferrin proteins?

The subdomains bend like a hinge when bound to iron Signup and view all the answers

What is the role of the bound carbonate in transferrin proteins?

It is hydrogen-bonded to side chains and the polypeptide backbone Signup and view all the answers

What is the function of lactoferrin, a member of the transferrin family?

To be present in milk Signup and view all the answers

What is the effect of high iron levels on the IRE-BP?

It decreases the affinity of IRE-BP for IREs Signup and view all the answers

What is the role of IRE-BP in ferritin mRNA translation?

It prevents the translation of ferritin mRNA Signup and view all the answers

What is the effect of low iron levels on the stability of transferrin receptor mRNA?

It increases the stability of transferrin receptor mRNA Signup and view all the answers

What is the molecular mass of the IRE-BP?

90 kilodaltons Signup and view all the answers

What is the homolog of the IRE-BP?

Mitochondrial aconitase Signup and view all the answers

What is the effect of iron on the cluster in the IRE-BP?

It forms the Fe,S4 cluster Signup and view all the answers

What is the role of the Fur protein in regulating gene expression?

It acts at the transcriptional level Signup and view all the answers

What is the function of the mercury detoxification system in bacteria?

It regulates the uptake, transport, and detoxification of mercury Signup and view all the answers

What is the effect of metal-ion concentration on the expression of genes involved in detoxification?

It regulates the expression of these genes Signup and view all the answers

What is the purpose of regulating metal-ion concentrations in cells?

To prevent the accumulation of toxic metals Signup and view all the answers

What is the first step in the process of mercury reduction by mercuric-ion reductase?

Hydride transfer from NADPH to flavin Signup and view all the answers

What is the role of the MerR protein in the mercury detoxification system?

It is a DNA-binding protein that senses mercury levels Signup and view all the answers

What happens to the DNA when mercury binds to the MerR protein?

It unwinds by 33 degrees Signup and view all the answers

What is the effect of increasing mercury concentration on the transcription of mercury detoxification genes?

It increases the rate of transcription more sharply than expected Signup and view all the answers

What is the concentration of mercury required to produce half the maximal rate of transcription?

10 nM Signup and view all the answers

What other metal ions can induce transcriptional activation of mercury detoxification genes?

Cd(II), Au(I), Zn(II), and Au(II) Signup and view all the answers

How many mercuric ions bind to each dimer of MerR protein?

One Signup and view all the answers

What is the likely binding mode of each mercury ion to the MerR protein?

One thiolate from one subunit and two from another Signup and view all the answers

What is the likely consequence of the binding of mercury to the MerR protein?

A change in the dimer conformation that is transmitted to the DNA Signup and view all the answers

What is the ultimate fate of the mercury atoms produced in the cell?

They are released into the environment Signup and view all the answers

What is the primary reason why mercuric ion is highly toxic to many organisms?

Its high affinity for thiols Signup and view all the answers

What is the function of the periplasmic binding protein in the bacterial system?

To pick up mercury compounds from the environment and deliver them to the transport protein Signup and view all the answers

What is the effect of organomercurial lyase on the hydrolysis rate of mercury-carbon bonds?

It accelerates the hydrolysis rate by approximately one million-fold Signup and view all the answers

What is the mechanism of action of organomercurial lyase?

A concerted &2 mechanism Signup and view all the answers

What is the product of the reaction catalyzed by organomercurial lyase?

A mercury thiolate adduct Signup and view all the answers

What is the function of mercuric ion reductase in the bacterial system?

To reduce mercuric ion to Hg(0) Signup and view all the answers

What is the main function of pumps in maintaining ionic gradients?

To generate and maintain ionic gradients Signup and view all the answers

What is the compromise that had to be struck in designing the active site of mercuric ion reductase?

Balancing the affinity for binding Hg(II) with the need to maintain a high redox potential Signup and view all the answers

What is the difference in potential between the two sides of a membrane?

Membrane potential Signup and view all the answers

What is the role of cysteine residues in the active site of mercuric ion reductase?

To coordinate the mercuric ion Signup and view all the answers

What is the significance of the crystal-structure analysis of the Cd(II) complex of a mercuric-ion reductase?

It suggests that the enzyme uses accessory nonthiolate ligands for substrate binding Signup and view all the answers

What determines the equilibrium potential for a particular ion?

The concentration differences according to the Nemst equation Signup and view all the answers

What is the ultimate product of the reactions catalyzed by organomercurial lyase and mercuric ion reductase?

Hg(0) Signup and view all the answers

What is the characteristic of channels that allows them to transduce information from one form to another?

Their gating ability Signup and view all the answers

What is the term for the ability of channels to transport specific ions with varying efficiency?

Ion selectivity Signup and view all the answers

What is the equation that relates the current conducted by a channel to the voltage across the membrane?

Ohm's law Signup and view all the answers

What is the function of pumps and channels in bioenergetics and nervous systems?

To store energy and information Signup and view all the answers

What is the term for the sum of the potentials due to each ion as determined by the differences in ion concentrations across the membrane?