INTRODUCTION
The entire cell in the
body must be supplied with essential substances like nutrient, water,
electrolyte, etc. The cells achieved these by means of transport mechanism
across the cell membrane. Two types of basic mechanisms are involved in the transport
of substances; these are active
transport mechanism and passive
transport mechanism.
Active transport follows a
mechanism whereby specialized integral proteins recognize the substance and
allow it access (or, in the case of secondary transport, expend energy on
forcing it) to cross the membrane when it otherwise would not, either because
it is one to which the phospholipids bilayer of the membrane is impermeable or
because it is moved against the direction of the concentration gradient. The
first case, known as PRIMARY active transport, showing proteins involved in it
as pumps, normally uses the chemical energy of ATP. Other cases, which usually
derive their energy through exploitation of an electrochemical gradient, are
known as SECONDARY and TERTIARY active transport which involve pore-forming
proteins that form channels through the cell membrane.
However, this
presentation will be focusing on active transport mechanism; with emphasis on
its types, examples, as well as diagrammatical description.
DEFINITION OF ACTIVE TRANSPORT:
Is the
movement of molecules across a
cell membrane in the direction against their
concentration gradient, i.e. moving from a low concentration to a high
concentration. Active transport is usually associated with accumulating high
concentrations of molecules that the cell needs, such as ions, glucose and amino
acids. It is also called uphill transport. Active transport requires
energy, which is obtained mainly by breakdown of high energy compounds like adenosine
triphosphate (ATP).
CARRIER
PROTEINS PATHWAY OF ACTIVE TRANSPORT
Carrier
proteins pathway involved in active transport are of two types:
1.
Uniport
2.
Symport
3. antiport.
1. UNIPORT:
Carrier
protein that carries only one substance in a single direction is called
uniport. It is also known as uniport pump.
2. SYMPORT
or ANTIPORT
Symport
or antiport is the carrier protein that transports two substances at a time.
Carrier protein that transports two different substances in the same direction
is called symport or symport
pump. Carrier protein that transports two different substances in opposite
directions is called antiport or antiport
pump.
MECHANISM
OF ACTIVE TRANSPORT
ATP hydrolysis is used to transport molecules against the electrochemical gradient (from low to high ionic concentration of the molecules). When a substance to be transported across the cell membrane comes near the cell, it combines with the carrier protein of the cell membrane and forms substance-protein complex. This complex moves towards the inner surface of the cell membrane, induce a conformational (shape) change that drives the substances to transport against the electrochemical gradient.
Then, the substance is released into the interstitial fluid (ICF) from the carrier proteins. The same carrier proteins move back to the outer surface of the cell membrane (i.e. restore back to its original conformation) to transport another molecule of the substance.
SUBSTANCE
TRANSPORTED BY ACTIVE TRANSPORT
Substances, which are transported
actively, are in ionic form 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.
TYPES OF ACTIVE TRANSPORT
Active
transport is of two major types:
1.
Primary active transport
2.
Secondary active transport.
However,
there is also occurrence tertiary active transport.
PRIMARY ACTIVE TRANSPORT
Primary active
transport, (also called direct active transport), directly uses metabolic
energy to transport molecules across a membrane. This energy in form adenosine
triphosphate (ATP) is hydrolyse to adenosine diphosphate (ADP) and liberating a
high-energy phosphate bond of energy. This is carried out by the carrier
protein ATPase, when activated by binding to a molecule.
Among the
substances that are transported by primary active transport are sodium,
potassium, calcium, hydrogen, chloride, and a few other ions.
EXAMPLES
OF PRIMARY ACTIVE TRANSPORT
In the transport of
ion, there are
§ primary
active transport of sodium/potassium (Na+/K+)
§ primary active transport of calcium (Ca+)
§ Primary
active transport of hydrogen (H+)
PRIMARY
ACTIVE TRANSPORT OF SODIUM AND POTASSIUM (sodium-potassium pump)
Sodium and potassium
ions are transported across the cell membrane by means of a common carrier
protein called sodium-potassium (Na+-K+) pump. It is also called Na+-K+ ATPase pump or Na+-K+ ATPase. This pump transports
sodium from inside to outside the cell and potassium from outside to inside the
cell. This pump is present in all the cells of the body. Na+-K+ pump is responsible for the
distribution of sodium and potassium ions across the cell membrane and the
development of resting membrane potential.
Structure of Na+ - K+ Pump
Carrier
protein that constitutes Na+-K+ pump is made up of two protein subunit
molecules, an α-subunit with a molecular weight of 100,000 and a β-subunit with
a molecular weight of 55,000. Transport of Na+ and K+ occurs only by α-subunit.
The β-subunit is a glycoprotein the function of which is not clear. α-subunit
of the Na+-K+ pump has got six sites:
i. Three receptor sites
for sodium ions on the inner (towards cytoplasm) surface of the protein
molecule
ii. Two receptor sites
for potassium ions on the outer (towards ECF) surface of the protein
molecule
iii. One site for
enzyme adenosine triphosphatase (ATPase), which is near the sites for sodium.
MECHANISM OF ACTION OF NA+-K+ PUMP
Three
sodium ions from the cell get attached to the receptor sites of sodium ions on
the inner surface of the carrier protein. Two potassium ions outside the cell
bind to the receptor sites of potassium ions located on the outer surface of
the carrier protein. (see fig. 1 above)
(Fig.
1). Diagrammatic illustration of Na+/K+
movement across the membrane.
Binding
of sodium and potassium ions to carrier protein activates the enzyme ATPase.
ATPase causes breakdown of ATP into adenosine diphosphate (ADP) with the
release of one high energy phosphate.
However,
the energy liberated causes some sort of conformational change in the molecule
of the carrier protein. Because of this, the outer surface of the molecule
(with potassium ions) now faces the inner side of the cell. And, the inner surface
of the protein molecule (with sodium ions) faces the outer side of the cell.
Dissociation
and release of the ions take place so that the sodium ions are released outside
the cell (ECF) and the potassium ions are released inside the cell (ICF). Exact
mechanisms involved in the dissociation and release of ions are not yet known.
Electrogenic activity of Na+-K+ pump
Na+-K+ pump moves three sodium ions outside
the cell and two potassium ions inside cell. Thus, when the pump works once,
there is a net loss of one positively charged ion from the cell. Continuous
activity of the sodium-potassium pumps causes reduction in the number of
positively charged ions inside the cell leading to increase in the negativity
inside the cell. This is called the electrogenic activity of Na+-K+ pump.
Importance of the Na+-K+ Pump
1. For Controlling
Cell Volume.
One of the most
important functions of the Na+-K+ pump is to control the volume of each cell.
Without function of this pump, most cells of the body would swell until they
burst. The mechanism for controlling the volume is as follows:
Inside the cell
are large numbers of proteins and other organic molecules that cannot escape
from the cell. Most of these are negatively charged and therefore attract large
numbers of potassium, sodium, and other positive ions as well. All these
molecules and ions then cause osmosis of water to the interior of the cell.
Unless this is checked, the cell will swell indefinitely until it bursts. The
normal mechanism for preventing this is the Na+K+ pump.
Note again that
this device pumps three Na+ ions to the outside of the cell for every two K+
ions pumped to the interior. Also, the membrane is far less permeable to sodium
ions than to potassium ions, so that once the sodium ions are on the outside,
they have a strong tendency to stay there.
Thus, this
represents a net loss of ions out of the cell, which initiates osmosis of water
out of the cell as well.
If a cell begins to
swell for any reason, this automatically activates the Na+-K+ pump, moving
still more ions to the exterior and carrying water with them. Therefore, the
Na+-K+ pump performs a continual surveillance role in maintaining normal cell
volume.
2. Generation of heat
in cell
Thyroid hormone stimulates
cells to produce more Na_-K_ pumps. As these pumps consume ATP, they release
heat, compensating for the body heat we lose to the cold air around us.
PRIMARY ACTIVE TRANSPORT OF CALCIUM IONS
Calcium is actively
transported from inside to outside the cell by calcium pump. Calcium pump is
operated by a separate carrier protein. Energy is obtained from ATP by the
catalytic activity of ATPase. Calcium pumps are also present in some organelles
of the cell such as sarcoplasmic reticulum in the muscle and the mitochondria
of all the cells. These pumps move calcium into the organelles.
PRIMARY ACTIVE TRANSPORT OF HYDROGEN IONS
Hydrogen ion is
actively transported across the cell membrane by the carrier protein called
hydrogen pump. It also obtains energy from ATP by the activity of ATPase. The
hydrogen pumps that are present in two important organs have some functional
significance.
1. Stomach: Hydrogen
pumps in parietal cells of the gastric glands are involved in the formation of hydrochloric
acid.
2.
Kidney: Hydrogen pumps in epithelial cells of distal convoluted tubules
and collecting ducts are involved in the secretion of hydrogen ions from blood
into urine .
SECONDARY ACTIVE TRANSPORT
In secondary active
transport, also known as coupled transport or co-transport,
energy is used to transport molecules across a membrane; however, in contrast
to primary
active transport, there
is no direct coupling of ATP;
instead, the electrochemical
potential difference created
by pumping ions out of the cell is used. Thus, it involves the transport of
sodium coupled with transport of another substance.
When sodium is
transported by a carrier protein, another substance is also transported by the
same protein simultaneously, either in the same direction (of sodium movement)
or in the opposite direction.
Secondary
active transport mechanism is of two types:
1. Co transport
2. Counter transport.
Mechanism of sodium co-transport
When sodium ions are
transported out of cells by primary active transport, a large concentration
gradient of sodium ions across the cell membrane usually develops high
concentration outside the cell and very low concentration inside. This gradient
represents a storehouse of energy because the excess sodium outside the cell
membrane is always attempting to diffuse to the interior. Under appropriate
conditions, this diffusion energy of sodium can pull other substances along
with the sodium through the cell membrane. This phenomenon is called co-transport.
For sodium to pull
another substance along with it, a coupling mechanism is required. This is
achieved by means of still another carrier protein in the cell membrane. The
carrier in this instance serves as an attachment point for both the sodium ion
and the substance to be co-transported. Once they both are attached, the energy
gradient of the sodium ion causes both the sodium ion and the other substance
to be transported together to the interior of the cell.
Sodium
co-transport of glucose
One sodium ion and one
glucose molecule from the extracellular fluid (ECF) bind with the respective receptor
sites of carrier protein of the cell membrane. Now, the carrier protein is
activated. It causes conformational changes in the carrier protein, so that
sodium and glucose are released into the cell (Fig. 3).
Sodium co-transport of
glucose occurs during absorption of glucose from the intestine and reabsorption
of glucose from the renal tubule.
Fig. 3 showing the
sodium-glucose cotransport
Sodium co-transport of amino acids
Carrier proteins
for the transport of amino acids are different from the carrier proteins for
the transport of glucose. For the transport of amino acids, there are five sets
of carrier proteins in the cell membrane. Each one carries different amino
acids depending upon the molecular weight of the amino acids.
Sodium co-transport of
amino acids also occurs during the absorption of amino acids from the intestine
and reabsorption from renal tubule.
TERTIARY ACTIVE TRANSPORT
This is 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:
1. 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−). Cl-base exchange is an
example of tertiary active
transport:
2. The apical Sodium - Proton exchange, itself
a secondary active transporter
provides the H+ that
neutralizes base in the lumen, thereby sustaining the gradient for Cl−anion
exchange. The basolateral exit step for transcellular Cl− movement may occur in part
through a Cl−channel that is analogous in
function to the cystic fibrosis transmembrane conductance regulator.
Figure 3. Showing the
tertiary active transport
( Fig 4.) Showing
illustration of primary, secondary and tertiary active transport movement.
REFRENCES:
Wikipedia; http://en.wikipedia.org/wiki/Active_transport#cite_ref-2
Essential
of medical pharmacology – k. sembulingam (6th edition)
Text
book of medical physiology ------ Guyton and Hall (11th
edition)
Anatomy
and physiology ------------------ Saladin
Mit
biology hypertexbook : http://dwb4.unl.edu/Chem/CHEM869K/CHEM869KLinks/esg
www.mit.edu/esgbio/cb/membranes/transport.htm
Wright
EM, Turk E (February 2004). "The sodium/glucose cotransport family
SLC5". Pflügers Arch. 447 (5): 510–8. doi:10.1007/s00424-003-1063-6.
PMID 12748858.
