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Subject Chemistry

Paper No and Title 15: Bioinorganic Chemistry

Module No and 8: Ion transport through cell membrane and Na+/K+

Title pump
Module Tag CHE_P15_M8

CHEMISTRY Paper No. 15: Bioinorganic Chemistry

Module No. 8: Ion transport through cell membrane and
Na+/K+ pump
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TABLE OF CONTENTS
1. Learning Outcomes
2. Introduction
3. Passive mediated transport
4. Active Transport
4.1 Na+-K+ -ATPase
4.2 Ca2+-ATPase
4.3 ABC transporters
5. Sodium potassium pump
6. Summary

CHEMISTRY Paper No. 15: Bioinorganic Chemistry

Module No. 8: Ion transport through cell membrane and
Na+/K+ pump
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1. Learning Outcomes
After studying this module, you shall be able to

 Learn about the mechanisms by which cells transport ions and small molecules across
their membranes.
 Know about the difference between facilitated diffusion and active transport of ions
across the cell membrane.
 Analyse the different types of ionophores use for transporting numerous molecules
through the cell membrane.
 Know about the various enzymes which work for active transporting of ions such as Na+-
K+ -ATPase, Ca2+-ATPase, ABC transporters and so on.
 Understand the detailed mechanism of Na+/K+ pump which is essential in creating
membrane potentials.

2. Introduction
The passive cation transport along a concentration gradient via a carrier mechanism proceeds
relatively slowly because of the necessary steps of complexation, migration and decomplexation.
A more efficient albeit biosynthetically more complex realization of controlled cation diffusion
consists in the integration of ion channels of various complexity into the fluid double layer of
biological phospholipid membranes. Due to the essential physiological importance of ion
channel, the external control of the ion-selective gates through development of suitable inhibitors
or stimulating agents has become one of the most active fields of pharmaceutical and medical
research.

There are two types of transport processes which exist in nature. These are nonmediated transport
and mediated transport. On one hand nonmediated transport occurs through simple diffusion
while in contrary the mediated transport occurs through the action of specific carrier proteins. The
driving force for the nonmediated flow of a substance through a medium is its chemical potential
gradient. Thus, the substance diffuses in the direction that eliminates its concentration gradient, at
a rate proportional to the magnitude of the gradient.

Depending on the thermodynamics of the system, the mediated transport is classified into two
categories (Figure 1):

1. Passive-mediated transport or facilitated diffusion – In this type of transport a specific

molecule flows from high concentration to low concentration.
2. Active transport – In this type of transport a molecule is transported from low
concentration to high concentration, that is, against its concentration gradient.

CHEMISTRY Paper No. 15: Bioinorganic Chemistry

Module No. 8: Ion transport through cell membrane and
Na+/K+ pump
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Figure 1: Facilitated diffusion and Active transport

3. Passive mediated transport

Substance that are too large or too polar to diffuse across lipid bilayers on their own may be
conveyed across membranes via proteins or other molecules that are variously called carriers,
permeases, channels and transporters.

Ionophores are multidentate (≥6) chelate ligands which either exist as macrocycles or can at least
quasi-macrocycles after coordination-induced ring closure via hydrogen bond interactions. There
are two types of ionophores (Figure 2):

1. Carrier ionophores - It increase the permeabilities of membranes to their selected ion by

binding it, diffusing through the membrane, and releasing the ion on the other side of the
membrane.
2. Channel – forming ionophores - which form transmembrane channels or pores through
which their selected ions can diffuse through the membrnae.

CHEMISTRY Paper No. 15: Bioinorganic Chemistry

Module No. 8: Ion transport through cell membrane and
Na+/K+ pump
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Figure 2: Two types of ionophores

Ionophores transport ions at a remarkable rate. For example, a single molecule of the carrier
ionophore valinomycin transports up to 104 K+ ions per second across a membrane (Figure 3).

Figure 3: Transport of K+ by valinomycin across a membrane

CHEMISTRY Paper No. 15: Bioinorganic Chemistry
Module No. 8: Ion transport through cell membrane and
Na+/K+ pump
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In channel proteins the gates are normally closed to guarantee the maintenance of the
concentration gradient. The opening of these gates can be influenced by exogeneous or
endogeneous low molecular weight compounds, by released Ca2+, by other protens, or by a
change in the electrical potential difference (voltage) across the membrane. Voltage-controlled
channels are thus biological switching elements which serve in the transformation of electrical
into chemical signals. The development of receptor-specific organic compounds for the blocking
of ion channel is one of the main targets of ‘molecular modeling’, on the other hand, the
unspecific blocking, e.g. of K+ channels by +N(C2H5)4, Cs+ or Ba2+, can be easily understood on
the basis of size and charge effects. The blocking of K+ channels in the taste receptors by H+ is
probably responsible for the sensing of ‘sour’.

4. Active transport
Passive mediated transporters, including porins, ion channels and proteins, facilitate the
transmembrane movements of substances according to the relative concentrations of the
substance on either side of the membrane. Many substances, however, are available on one side
of a membrane in lower concentrations than are required on the other side of the membrane. Such
substances must be actively and selectively transported across the membrane against their
concentration gradients. Active transport is an endergonic process that, in most cases, is coupled
to the hydrolysis of ATP.

4.1 Na+-K+ -ATPase

One of the most thoroughly studied active transport systems is the Na+-K+ -ATPase in the plasma
membranes of higher eukaryotes, which was first characterized by Jens Skou. This
transmembrane protein consists of two types of subunits: a 110-kD nonglycosylated α subunit
that contains the enzymes’s catalytic activity and ion-binding sites, and a 55-kD glycoprotein β
subunit of unknown function. The Na+-K+ -ATPase is often called the (Na+-K+) pump because it
pumps Na+ out of and K+ into the cell with the concomitant hydrolysis of intracellular ATP. This
extrusion of Na+ enables animal cells to control their water content osmotically: without
functioning Na+-K+ -ATPase to maintain a low internal [Na+], water would osmotically rush in to
such an extent that animal cells, which lack cell walls, would swell and burst. The
electrochemical gradient generated by the Na+-K+ -ATPase is also responsible for the electrical
excitability of nerve cells. The detailed mechanism as to how this sodiym potassium pump works
is explain in the next section.

4.2 Ca2+-ATPase

Transient increases in cytosolic Ca2+ trigger numerous cellular responses including muscle
contraction, the release or neurotransmitters, and glycogen breakdown. Moreover Ca 2+ is an
important activator of oxidative metabolism. The [Ca2+] in the cytosol (0.1 µM) is four orders of
magnitude less than it is in the extracellular spaces. This large concentration gradient is
maintained by the active transport of Ca2+ across the plasma membrane and the endoplasmic
reticulum by a Ca2+-ATPase (Figure 4). This Ca2+ pump actively pumps two Ca2+ ions out of the

CHEMISTRY Paper No. 15: Bioinorganic Chemistry

Module No. 8: Ion transport through cell membrane and
Na+/K+ pump
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cytosol at the expense of ATP hydrolysis, while countertransporting two or three protons. The
mechanism of the Ca2+-ATPase resembles that of the Na+-K+ -ATPase.

Figure 4: Ca2+ pump

4.3 ABC transporters

The ABC transporters, which pump ions, sugars, amino acids, and other polar and nonpolar
substances, are built from four modules: two highly conserved cytoplasmic nucleotide-binding
domains, and two transmembrane domains that typically contain six transmembrane helices each.
Bacterial ABC transporters mediate the uptake as well as the efflux of a variety of compounds,
whereas their eukaryotic counterparts apparently operate only as exporters that transport material
out of the cell or into intracellular compartments such as the endoplasmic reticulum.

5. Sodium potassium pump

The best known ion pump is the Na+/K+ - ATPase, a major component of the sodium/potassium
pump system which is essential in creating membrane potentials. ATP stores energy for the cell in
the form of free energy that can be released on hydrolysis of the P-O-P phosphate bond of the
phosphate polymer. The suitable pH and required charge gradient are created across a cell
membrane by the reactions that exploit the electron acceptor properties of the O2 molecule, which
is ultimately responsible for building up the energy carrier of the cell.

CHEMISTRY Paper No. 15: Bioinorganic Chemistry

Module No. 8: Ion transport through cell membrane and
Na+/K+ pump
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The high concentration gradient of Na+ and K+ that exist across the cell membrane are maintained
by the activity of an energy-requiring pump that transports Na+ out of the cell in exchange for K+
ions inside the cell membrane than outside, and a higher concentration of Na+ outside the cell
than inside. The energy for pumping is provided by ATP generated during metabolic reactions in
the cell. In the erythrocyte cell, three Na+ are pumped outward and two K+ inwards for each
molecule of ATP hydrolysed to ADP and inorganic phosphate.

Sodium and potassium ion-activated adenosine triphosphatase is a complex, membrane-bound

enzyme that catalyzes the transport of three sodium ions out of the cell and two potassium ions
into the cell with associated hydrolysis of MgATP. The mechanism of the sodium pump requires
an account of the role of lipid, the binding sites for Na+, K+, Mg2+ and ATP, the mechanism of
hydrolysis of ATP and the way in which this is coupled to the transport of the cation. Based on
the reaction sequences, the mechanism can be outlined (Figure 5). Firstly ATP and three Na+ ions
bind to inside of the membrane and the enzyme is phosphorylated in the presence of Na + and
Mg2+ to give a phosphoenzyme.This enzyme undergoes eversion followed by dephosphorylation
in a K+ dependent process and three Na+ ions are replaced by two K+. The loss of ATP triggers
conformational change and carries the two K+ ions into the interior of cell where they are
released. The cycle is thus complete and enzyme is again available for phosphorylation. This
process builds up a charge gradient across the membrane because three Na + are expelled for two
K+ ions incorporated and therefore outer surface becomes relatively positively charged.

Figure 5: Mechanism of sodium potassium pump

CHEMISTRY Paper No. 15: Bioinorganic Chemistry

Module No. 8: Ion transport through cell membrane and
Na+/K+ pump
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The activity of the Na+-K+ ATPase appears to be linked to the uptake of a variety of solutes by
tissues, using carrier molecules that facilitate the specific and compulsory cotransport of Na+ and
the solute molecule. When the external Na+ ion concentration is maintained much higher than the
internal Na+ concentration by the Na+/K+ pump, Na+ and solute bound to carrier and will move
inward, down the Na+ concentration gradient.

6. Summary
 The passive cation transport along a concentration gradient via a carrier mechanism
proceeds relatively slowly because of the necessary steps of complexation, migration
and decomplexation.
 Active transport is an endergonic process that, in most cases, is coupled to the
hydrolysis of ATP.
 One of the most thoroughly studied active transport systems is the Na+-K+ -ATPase
in the plasma membranes of higher eukaryotes, which was first characterized by Jens
Skou.
 The large concentration gradient is maintained by the active transport of Ca 2+ across
the plasma membrane and the endoplasmic reticulum by a Ca2+-ATPase.
 Bacterial ABC transporters mediate the uptake as well as the efflux of a variety of
compounds, whereas their eukaryotic counterparts apparently operate only as
exporters that transport material out of the cell or into intracellular compartments
such as the endoplasmic reticulum.
 The best known ion pump is the Na+/K+ - ATPase, a major component of the
sodium/potassium pump system which is essential in creating membrane potentials.
 In the erythrocyte cell, three Na+ are pumped outward and two K+ inwards for each
molecule of ATP hydrolysed to ADP and inorganic phosphate.
 The activity of the Na+-K+ ATPase appears to be linked to the uptake of a variety of
solutes by tissues, using carrier molecules that facilitate the specific and compulsory
cotransport of Na+ and the solute molecule.

CHEMISTRY Paper No. 15: Bioinorganic Chemistry

Module No. 8: Ion transport through cell membrane and
Na+/K+ pump