Active Transport Mechanism

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ACTIVE TRANSPORT MECHANISM

PRIMARY ACTIVE TRANSPORT

SECONDARY ACTIVE TRANSPORT

TERTIARY ACTIVE TRANSPORT

AND

SODIUM POTASSIUM PUMP


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PRESENT


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OUTLINE


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TERMINOLOGIES


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INTRODUCTION

The plasma membrane is both a barrier and gateway between the cytoplasm and the extracellular fluid.

It is selective permeable i.e. allows some substances to pass through it such as nutrients and wastes but

usually prevent other substance such as proteins and phosphates from entering or leaving the cells.

All the cells in the body must be supplied with essential substances like nutrients, water, electrolytes, etc.

Cells also must get rid of many unwanted substances like carbon dioxide in order for the cell to survive.

The cells achieve these by means of transport mechanisms across the cell membrane.

Two types of mechanisms are involved in transport of substances across the cell membrane. These arepassive and active transport.

Passive transport is the movement of substances along the concentration gradient or electrical gradient. It

does not require energy expenditure of the cell. In most cases the random molecular motion of the

particles themselves provide the necessary energy . Examples include simple diffusion, osmosis, filtration

and facilitated diffusion which is carrier mediated.

Active transport mechanism however consumes energy in form adenosine triphosphate, example include

active transport and vesicular transport. Example of active transport is the sodium-potassium (Na-K) pump, also known as Na-KATPase because

the carrier is an enzyme that hydrolyzes ATP.


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Fig.1 diagrammatic representation of membrane transport.


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ACTIVE TRANSPORT

Active transport is the carrier-mediated transport of Substancesthrough a membrane against the concentration gradient orelectrical gradient.

It is also referred to as uphill transport of substances since its amovement against the concentration gradient.

Movement of the transported substance to the opposite side of themembrane and its subsequent release from the carrier protein arefueled by the breakdown of ATP.

The maximum rate at which active transport proceeds depends onthe number of carrier proteins in the plasma membrane and theavailability of adequate ATP.

It is usually associated with accumulating high concentrations ofmolecules that the cell needs, such as ions, glucose and amino acids


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Examples;

. Examples of active transport include the

transportation of sodium out of the cell and

potassium into the cell by the sodium-

potassium pump.

Active transport often takes place in the

internal lining of the small intestine.


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Carrier proteins involved in active

transport;

Carrier protein of active transport can be

uniporter

symporter

antiporter.


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Fig.2: diagrammatic representation of carrier proteins involved

in active transport.


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uniporter It is an integral

membrane protein

which is involved in

the movement of

one type ofmolecule or ion

across the plasma

membrane


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Antiporter is an integral

membrane protein

which is involved in

movement of two or

more different

molecules or ionsacross a as the plasma

membrane in opposite

directions.

Example is the Na-K

pumps


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Symporter It is an integral

membrane proteinwhich is involved inmovement of two ormore different

molecules or ionsacross the plasmamembrane in thesame direction.

Example is the

sodium glucosetransporter in theabsorptive cells of thesmall intestine andrenal tubules


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FEATURES OF ACTIVE TRANSPORT

Substances, which are transported actively, are in ionicand non-ionic form. Substances in ionic form aresodium, potassium, calcium, hydrogen, chloride andiodide. Substances in non-ionic form are glucose,

amino acids and urea. It is carrier mediated

Its uphill

It requires energy which is derived mainly from thebreakdown of ATP

It occurs in all human cells.

Process can be modified by drugs such as ouabain,aspirin


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TYPES OF ACTIVE TRANSPORT

Primary active transport

Secondary active transport

Tertiary active transport


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PRIMARY ACTIVE TRANSPORT

This is the type of active transport in which the energy is deriveddirectly from the breakdown of adenosine triphosphate (ATP) withthe process. Ions such as sodium, potassium, calcium, hydrogen,chloride etc. are transported across the plasma membrane.

Most of the enzymes that perform this type of transport are trans-

membrane ATPase A primary ATPase universal to all animal life is the sodium-

potassium pump, which helps to maintain the cell potential.

Other sources of energy for Primary active transportare redox energy. An example of primary active transport usingRedox energy is the mitochondrial electron transport chain that

uses the reduction energy of NADH to move protons across theinner mitochondrial membrane against their concentrationgradient.


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OTHER EXAMPLES;


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PRIMARY ACTIVE TRANSPORT OF CALCIUM

IONS:

Calcium ions are normally maintained at extremely low concentration in

the intracellular cytosol of virtually all cells in the body, at a concentration

about 10,000 times less than that in the extracellular fluid.

This is achieved mainly by two primary active transport calcium pumps.

One is in the cell membrane and pumps calcium to the outside of the cell.

The other pumps calcium ions into one or more of the intracellular

vesicular organelles of the cell, such as the sarcoplasmic reticulum of

muscle cells and the mitochondria in all cells.

In each of these instances, the carrier protein penetrates the membrane

and functions as an enzyme ATPase, having the same capability to cleaveATP as the ATPase of the sodium carrier protein.

The difference is that this protein has a highly specific binding site for

calcium instead of for sodium.


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Fig.3: Active transport of calcium ions


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PRIMARY ACTIVE TRANSPORT OF


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PRIMARY ACTIVE TRANSPORT OF

HYDROGEN IONS:

Primary active transport of hydrogen ions at

two places in the body,

In the gastric glands of the stomach.

In the late distal tubules and cortical

collecting ducts of the kidneys.


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Fig.5:Primary active transport of hydrogen ions


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SECONDARY ACTIVE TRANSPORT

This is the type of active transport in which

the energy is derived secondarily from energy

that has been stored in the form of ionic

concentration differences of secondarymolecular or ionic substances between the

two sides of a cell membrane, created

originally by primary active transport.


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forms of secondary active transport

Co- transport

Counter transport


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Fig.6: Secondary Active TransportCo-Transport and Counter-Transport


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CO-TRANSPORT

The concentration gradient developed fromthe primary active transport of sodium ionsserves as a storehouse of energy because the

excess sodium outside the cell membrane isalways attempting to diffuse to the interior.

This diffusion energy of sodium pulls othersubstances (e.g. glucose, amino acids) alongwith the sodium through the cell membrane.

This phenomenon is called co-transport.


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SODIUM GLUCOSE TRANSPORT

The transport carrier protein has two binding sites on itsexterior side, one for sodium and one for glucose.

Due to the very high concentration of sodium ions on theoutside and very low inside, energy is provided for thetransport.

A special property of the transport protein is that aconformational change to allow sodium movement to theinterior will not occur until a glucose molecule alsoattaches.

When they both become attached, the conformationalchange takes place automatically, and the sodium andglucose are transported to the inside of the cell at the sametime.


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Fig.7: diagrammatic representation of sodium glucose

transport


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Counter transport

In counter-transport, sodium ions again attempt to diffuseto the interior of the cell because of their largeconcentration gradient.

However, this time, the substance to be transported is onthe inside of the cell and must be transported to theoutside.

Therefore, the sodium ion binds to the carrier proteinwhere it projects to the exterior surface of the membrane,while the substance to be counter-transported binds to theinterior projection of the carrier protein.

Once both have bound, a conformational change occurs,and energy released by the sodium ion moving to theinterior causes the other substance to move to the exterior.


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Tertiary transport

This is the type of active transport in which

the energy is derived from energy that has

been stored in the form of ionic concentration

differences from secondary active transport ofsubstances between the two sides of a cell

membrane, created originally by primary

active transport.


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EXAMPLE OF TERTIARY ACTIVE

TRANSPORT

In the transcellular reabsorption of Clin the

late proximal tubule where the energetically

uphill influx of Clacross the apical membrane

occurs through an exchange of luminal Clforcellular anions (e.g., formate, oxalate, HCO3

,

and OH).


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Fig.8: diagrammatic representation of tertiary active

transport.


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SODIUM-POTASSIUM ATPase

Sodium-potassium (Na-K) pump is an electrogenic pumpthat actively transports sodium ions outward through thecell membrane of all cells and at the same time pumpspotassium ions from the outside to the inside.

It is responsible for;

I. maintaining the sodium and potassium concentrationdifferences across the cell membrane,

II. as well as for establishing a negative electrical voltageinside the cells which is also the basis of nerve function,transmitting nerve signals throughout the nervous

system. It is responsible for cells containing relatively high

concentrations of potassium ions but low concentrationsof sodium ions.


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DISCOVERY

Na+/K+-ATPase was discovered by Jens

Christian Skou in 1957 while working as

assistant professor at the Department of

Physiology, University of Aarhus, Denmark.


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STRUCTURE:

The carrier protein is a complex of two separateglobular proteins: a larger one called the subunit,(approx. 1000 amino acids) with amolecular weight of about 100,000 and a smaller

one called the subunit, (approx.305 aminoacids), with a molecular weight of about 55,000.Although the function of the smaller protein isnot known (except that it might anchor the

protein complex in the lipid membrane), thelarger protein has three specific features that areimportant for the functioning of the pump


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Fig.9: structure of NaKATPase


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Structure contd

It has three receptorsites for binding sodium

ions on the portion of the

protein that protrudes to

the inside of the cell.

It has two receptor sitesfor potassium ions on the

outside.

The inside portion of

this protein near the

sodium binding sites hasATPase activity.


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Fig.10: MECHANISM OF ACTION OF Na+/K+ATPase

ELECTROGENIC NATURE OF THE NAK


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ELECTROGENIC NATURE OF THE NA K

PUMP.

the Na-K pump is said to be electrogenicbecause it creates an electrical potential acrossthe cell membrane.

The fact that the Na-K pump moves three Na

ions to the exterior for every two K ions to theinterior, means that a net of one positive chargeis moved from the interior of the cell to theexterior for each cycle of the pump.

This creates positivity outside the cell but leavesa deficit of positive ions inside the cell; that is, itcauses negativity on the inside.


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REGULATION:

Endogenous regulation

Exogenous regulation


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ENDOGENOUS

The Na+/K+-ATPase is upregulated by cAMP.

Thus, substances causing an increase in cAMP

upregulate the Na+/K+-ATPase. These include

the ligands of the Gs-coupled GPCRs.

In contrast, substances causing a decrease in

cAMP downregulate the Na+/K+- ATPase.

These include the ligands of the Gi-coupledGPCRs.

EXOGENOUS


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EXOGENOUS

The Na

+

/K

+

-ATPase can be pharmacologicallymodified by administrating drugs exogenously.

E.g. digoxinand ouabain
http://en.wikipedia.org/wiki/Digoxinhttp://en.wikipedia.org/wiki/Ouabainhttp://en.wikipedia.org/wiki/Ouabainhttp://en.wikipedia.org/wiki/Digoxin


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FUNCTIONS

Na+/K+- ATPase helps maintain resting

potential,

avail transport,

regulate cellular volume

Functioning as signal transducer:

Controlling neuron activity states:

Heat production:


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RESTING POTENTIAL

Na+/K+- ATPase, as well as effects of diffusion of theinvolved ions maintain the resting potential across themembranes.

In order to maintain the cell membrane potential, cellskeep a low concentration of sodium ions and high levels ofpotassium ions within the cell (intracellular). The sodium-potassium pump moves 3 sodium ions out and moves 2potassium ions in, thus, in total, removing one positivecharge carrier from the intracellular space.

The action of the sodium-potassium pump is not the only

mechanism responsible for the generation of the restingmembrane potential. Also, the selective permeability of thecell's plasma membrane for the different ions plays animportant role.


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Active Transport Mechanism

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