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Metal Ion Transport and Storage

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Bio Inorganic Chemistry Presentation 01

Group Members.• H.T.P. Dayananda.• A.K.A. Perera.• H.S. Alwis.• S.L. Weerasinghe.• K.G. Sapumohotti

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OUTLINE

• Metal Ions Bioavailability.• General Properties of Transport Systems.• Mechanisms of metal ion storage & resistance.• Specific Metal Ions

– K / Na– Fe– Ca

• Problems of Metal Ion Transport.

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Introduction

• Chemical Properties.– Catalyze oxidation & reduction. eg:Cu– Act as Lewis acid in hydrolytic enzymes. eg: Zn– Structural Co-factor.

• Problems.– Genetic diseases.

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Metal Ion Bioavailability.

• Bioavailability term implies more than just the incidence of an element on Earth and includes its prevalence in environment where life is found.

– Nickel in the Earth's core.– Zinc sulfide in the biosphere.– Molybdenum in the ocean

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Bioavailability.

• Fe is fourth most abundent element in Earth’s crust.

• For mammalian cells,the source of metal ions is the blood plasma.

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General properties of transport systems.

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Ionophores

special carrier molecules that wrap around metal ions.

Pass through the membrane by diffusion.

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Ion Channels

Large pores in membrane.Allow to movement of substrate across by

diffusion.

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Ion Channels.

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Ion pumps

Molecules using energy to transport ions in one direction through a membrane.

Primary active transport system.

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Carriers

Bind to substrate on one side of membrane.

Confrmatinal change.

Release the substrate on opposite side of membrane.

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Carriers

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Mechanisms for membrane Transport.

• Passive Transport :Movement of ions.Due to concentration gradient.Requiring no energy source.Ionophores , Ion channels.

• Active Transport :Movement of ions.Against the concentration gradient.Requiring energy from ATP hydrolysis.Ion pumps.

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Metal ion storage & Resistance

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Mechanisms of metal ion storage & resistance

• Organisms store metal ions.• It have more benefits.

• Allow the accumulation of high intacellular lebels of metal ions without the toxic.

• Understood mechanis of metal ion storage are,

FerritinMetallothionein

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Ferritin

• Ferritin are disscussed in greater detail under Iron Storage.

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Metallothionein

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Metallothionein

• cytopalmic metal- binding protein.• Involved in ion storage & detoxification.• Small ,cysteine-rich proteins that bind

Zn2+,Cd2+ Cu2+ & cys ligands.• Found in cyanobacteria,fungi,plants ,insects &

vertebrates.• Bind metal ions with high affinity.

Sodium -Na+

• Major cation in human body• Important for– membrane function– Nerve impulses– Muscle contraction– Prevent blood clotting

• Present in stomach walls, gallbladder and

Potassium- K+

• Important for– Membrane function– Maintaining osmotic balance– Cofactor in photosynthesis and respiration

Sodium &Potassium

• Concentration of [Na+] &[K+] – Inside red blood cells [Na+]

=0.01M [K+] =0.09M– Outside red blood cells [Na+]

=0.16M [K+] =0.01M

• Ion pump is required to maintain concentration gradient

• Also– Ionphore– Ion channel are used for Na &

K ion transport

Na -K Pump

Mechanism of Na+ –K+ pump

Sodium –Potassium Pump

• Na+ /K+ - ATPase -ATP + 3Na+

– Phosphorylation of enzyme– Eversion & releasing Na+

– Binding of 2K+

– Dephosphorylation– Eversion & releasing K+

• 3Na+ + 2K+ +ATP4- +H2O 3Na+ + 2K+ +ATP3- +H3PO 4

3- + H +

Selectivity of the process

• Depends upon– Differences in ionic radii.– Coulomb forces

• Bases stronger than H2O – bind preferentially to the hard acid Na

• Bases weaker than H2O – bind preferentially to the hard acid K

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Iron

• Most abundant transition element.• Involve in many biological roles.

e.g. oxygen transport.electron transport.metabolism.

• Versatility : Fe2+ / Fe3+

High spin / low spinHard / softLabile / inertCo-ordination number 4 , 5, 6

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Transport of iron

• Organisms mobilize Fe.• Three general ways which mobilization is

accomplished.Chelation.Reduction.Acidification.

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chelation

Bacteria, fungi, and some plants use chelating agents called “siderophores” to obtain ions.

Siderophores : Small molecules released into the environment.Complexation of fe3+ solubilizes its for uptake.Ligands are catechol and hydroxamic acid

chelates.

Mainly 3 examples.

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Siderophores

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Iron

• Enterobactin : 3 catechol chelates bound to a 1 membered ring.Complex anion is soluble.

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iron

• ferrichromes :• 3 hydroxamic acids, cyclic peptide.

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iron

• Ferrioxamines :• 3 hydroxamic acids , acyclic peptide.

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Reduction

• Reduce extracellular fe3+ to fe2+

• Reduction increase solubility & support the transportation of particular Fe.

• Reduction of Fe3+ mediated by “ferrireductases”

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Acidification.

• Conjuction with reduction dependent pathways.

• Acidify extracellular environment.• Increase the soluble ferric concentation by

inbiting formation of hydrolysis prducts [Fe(OH)3]

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Mammalian iron transport.

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Mammalian iron transport

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Receptor mediated endocytsis

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Transferrin

• 700 amino acid serum protein which has higher affinity towards ferric ions.

Synthesized in liver.Secreted into the plasma.From a chelate complex.

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Transferrin

• Transferrin : mammelian transport αβ dimer protein.– Ironcaptured as Fe2+ & oxidized to Fe3+

– Co32- ust bind at same time ; Synergism.

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Transferrin

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Mammalian Iron Storage

• FerritinFound in vertebrates , plants , fungi & bacteria.

Primary site of Fe storage.

It has outer coat of protein an inner core of hydrous ferric oxide.

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Ferritin

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Ferritin

• The iron strorage protein.– Ferritin is a protein, store iron & release it in a

controlled fashion.– If the blood has too little iron, ferritin can release

more.– If the blood or tissues of body have too much iron,

ferritin can help to store the excess iron.

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Ferritin

• Ferritin is synthesized as needed.– Normal iron load is 3 – 5 grams in human.– Ferritin is stored in cell in the bone marrow,liver &

spleen.– Siderosis : iron overload

» Deposits in liver, kidneys & heart» Treated by chelation therapy. (desferrioxamine)

Calcium

• Present in bones, enamel, shells• Important for– Signal pathways– Skeletal material– Maintaining potential difference across

membranes• Concentration– Outside cell = 0.001M– Inside cell = 10-7 M

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Calcium Regulaton.

Calcium storage

• Egg shells. Coral skeleton –CaCO3

• Bones & teeth – Calcium Hydroxyapatite in collagen– Collagen – triple helix fibrous protein– Hydroxyapatite-around collagenIf required Ca2+ can be released and reabsorbed.

Calcium pump

• Ca is in cytoplasm.• pumped in to sarcoplasmic reticulum (A form of

endoplasmic reticulum) • Up to 0.03M• Inside SR Ca is bound by calsequestrin• Hormone induced ion channels releases Ca

from SR to muscle cell• Muscle contraction is triggered by sudden

release of Ca

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Calcium pump

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Transport & storage problems.

• Capture of trace ions from the environment– Control the concentration.– Bulk ones present in high concentration.– Trace ones actively accumulated &insoluble.

• Selectivity of ion uptake is essential.– Toxic ions excluded.– Beneficial ions accumulated.– Specialized molecules have evolved.

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Transport & storage problems.

• Charged ions pass through a Hydrophobic Membrane.

• Neutral gases & low charge density ions move directly but high charge density require help.

• Metal ions transport to their location for use & storage.

• Release from ligand & storage require additional molecules.

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