ACTIVE TRANSPORT MECHANISM

PRIMARY ACTIVE TRANSPORT

SECONDARY ACTIVE TRANSPORT
TERTIARY ACTIVE TRANSPORT

AND

SODIUM POTASSIUM PUMP

PRESENT

OUTLINE

TERMINOLOGIES

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 are
passive 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.

Fig.1 diagrammatic representation of membrane transport.

ACTIVE TRANSPORT
Active transport is the carrier-mediated transport of Substances
through a membrane against the concentration gradient or
electrical gradient.
It is also referred to as uphill transport of substances since its a
movement against the concentration gradient.
Movement of the transported substance to the opposite side of the
membrane and its subsequent release from the carrier protein are
fueled by the breakdown of ATP.
The maximum rate at which active transport proceeds depends on
the number of carrier proteins in the plasma membrane and the
availability of adequate ATP.
It is usually associated with accumulating high concentrations of
molecules that the cell needs, such as ions, glucose and amino acids

Examples;
. Examples of active transport include the
transportation of sodium out of the cell and
potassium into the cell by the sodiumpotassium pump.
Active transport often takes place in the
internal lining of the small intestine.

Carrier proteins involved in active

transport;
Carrier protein of active transport can be
uniporter
symporter
antiporter.

Fig.2: diagrammatic representation of carrier proteins involved

in active transport.

uniporter
It is an integral
membrane protein
which is involved in
the movement of
one type of
molecule or ion
across the plasma
membrane

Antiporter
is an integral
membrane protein
which is involved in
movement of two or
more different
molecules or ions
across a as the plasma
membrane in opposite
directions.
Example is the Na-K
pumps

Symporter
It is an integral
membrane protein
which is involved in
movement of two or
more different
molecules or ions
across the plasma
membrane in the
same direction.
Example is the
sodium glucose
transporter in the
absorptive cells of the
small intestine and
renal tubules

FEATURES OF ACTIVE TRANSPORT

Substances, which are transported actively, are in ionic
and non-ionic form. Substances in ionic form are
sodium, potassium, calcium, hydrogen, chloride and
iodide. 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 the
breakdown of ATP
It occurs in all human cells.
Process can be modified by drugs such as ouabain,
aspirin

TYPES OF ACTIVE TRANSPORT

Primary active transport
Secondary active transport
Tertiary active transport

PRIMARY ACTIVE TRANSPORT

This is the type of active transport in which the energy is derived
directly from the breakdown of adenosine triphosphate (ATP) with
the 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 transmembrane ATPase
A primary ATPase universal to all animal life is the sodiumpotassium pump, which helps to maintain the cell potential.
Other sources of energy for Primary active transport
are redox energy. An example of primary active transport using
Redox energy is the mitochondrial electron transport chain that
uses the reduction energy of NADH to move protons across the
inner mitochondrial membrane against their concentration
gradient.

OTHER EXAMPLES;

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 uid.
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 cleave
ATP as the ATPase of the sodium carrier protein.
The difference is that this protein has a highly specic binding site for
calcium instead of for sodium.

Fig.3: Active transport of calcium ions

Fig.4: Active transport of calcium ions

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.

Fig.5:Primary active transport of hydrogen ions

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 secondary
molecular or ionic substances between the
two sides of a cell membrane, created
originally by primary active transport.

forms of secondary active transport

Co- transport
Counter transport

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

CO-TRANSPORT
The concentration gradient developed from
the primary active transport of sodium ions
serves as a storehouse of energy because the
excess sodium outside the cell membrane is
always attempting to diffuse to the interior.
This diffusion energy of sodium pulls other
substances (e.g. glucose, amino acids) along
with the sodium through the cell membrane.
This phenomenon is called co-transport.

SODIUM GLUCOSE TRANSPORT

The transport carrier protein has two binding sites on its
exterior side, one for sodium and one for glucose.
Due to the very high concentration of sodium ions on the
outside and very low inside, energy is provided for the
transport.
A special property of the transport protein is that a
conformational change to allow sodium movement to the
interior will not occur until a glucose molecule also
attaches.
When they both become attached, the conformational
change takes place automatically, and the sodium and
glucose are transported to the inside of the cell at the same
time.

Fig.7: diagrammatic representation of sodium glucose

transport

Counter transport
In counter-transport, sodium ions again attempt to diffuse
to the interior of the cell because of their large
concentration gradient.
However, this time, the sub- stance to be transported is on
the inside of the cell and must be transported to the
outside.
Therefore, the sodium ion binds to the carrier protein
where it projects to the exterior surface of the membrane,
while the substance to be counter-transported binds to the
interior projection of the carrier protein.
Once both have bound, a conformational change occurs,
and energy released by the sodium ion moving to the
interior causes the other substance to move to the exterior.

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 of
substances between the two sides of a cell
membrane, created originally by primary
active transport.

EXAMPLE OF TERTIARY ACTIVE

TRANSPORT
In the transcellular reabsorption of Cl in the
late proximal tubule where the energetically
uphill influx of Cl across the apical membrane
occurs through an exchange of luminal Cl for
cellular anions (e.g., formate, oxalate, HCO3,
and OH).

Fig.8: diagrammatic representation of tertiary active

transport.

SODIUM-POTASSIUM ATPase
Sodium-potassium (Na-K) pump is an electrogenic pump
that actively transports sodium ions outward through the
cell membrane of all cells and at the same time pumps
potassium ions from the outside to the inside.
It is responsible for;
I.
maintaining the sodium and potassium concentration
differences across the cell membrane,
II. as well as for establishing a negative electrical voltage
inside 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 concentrations
of sodium ions.

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.

STRUCTURE:
The carrier protein is a complex of two separate
globular proteins: a larger one called the
subunit,(approx. 1000 amino acids) with a
molecular weight of about 100,000 and a smaller
one called the subunit, (approx.305 amino
acids), with a molecular weight of about 55,000.
Although the function of the smaller protein is
not known (except that it might anchor the
protein complex in the lipid membrane), the
larger protein has three specic features that are
important for the functioning of the pump

Fig.9: structure of NaKATPase

Structure contd
It has three receptor
sites for binding sodium
ions on the portion of the
protein that protrudes to
the inside of the cell.
It has two receptor sites
for potassium ions on the
outside.
The inside portion of
this protein near the
sodium binding sites has
ATPase activity.

MECHANISM OF ACTION OF Na+/K+ ATPase:

The pump, while binding ATP, binds 3 intracellular Na+ ions.
ATP is hydrolyzed, leading to phosphorylation of the pump at a
highly conserved aspartate residue and subsequent release of ADP.
A conformational change in the pump exposes the Na+
ions to the outside. The phosphorylated form of the pump has a
low affinity for Na+ ions, so they are released.
The pump binds 2 extracellular K+ ions. This causes
the dephosphorylationof the pump, reverting it to its previous
conformational state, transporting the K+ ions into the cell.
The unphosphorylated form of the pump has a higher affinity
for Na+
ions than K+ ions, so the two bound K+ ions are released. ATP
binds, and the process starts again.

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

ELECTROGENIC NATURE OF THE NAK

PUMP.
the Na-K pump is said to be electrogenic
because it creates an electrical potential across
the cell membrane.
The fact that the Na-K pump moves three Na
ions to the exterior for every two K ions to the
interior, means that a net of one positive charge
is moved from the interior of the cell to the
exterior for each cycle of the pump.
This creates positivity outside the cell but leaves
a decit of positive ions inside the cell; that is, it
causes negativity on the inside.

REGULATION:
Endogenous regulation
Exogenous regulation

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-coupled
GPCRs.

EXOGENOUS
The Na+/K+-ATPase can be pharmacologically
modified by administrating drugs exogenously.
E.g. digoxin and ouabain

FUNCTIONS
Na+/K+- ATPase helps maintain resting
potential,
avail transport,
regulate cellular volume
Functioning as signal transducer:
Controlling neuron activity states:
Heat production:

RESTING POTENTIAL
Na+/K+- ATPase, as well as effects of diffusion of the
involved ions maintain the resting potential across the
membranes.
In order to maintain the cell membrane potential, cells
keep a low concentration of sodium ions and high levels of
potassium ions within the cell (intracellular). The sodiumpotassium pump moves 3 sodium ions out and moves 2
potassium ions in, thus, in total, removing one positive
charge carrier from the intracellular space.
The action of the sodium-potassium pump is not the only
mechanism responsible for the generation of the resting
membrane potential. Also, the selective permeability of the
cell's plasma membrane for the different ions plays an
important role.