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Presented by: Husna zaheer
MS Inorganic chemistry
Lahore College for Women University
SODIUM POTASSIUM
PUMPS
BIOINORGANIC CHEMISTRY
Contents:
History
Introduction
Structure
Forms of sodium - potassium pump
Mechanism
The Electrochemical Gradient
Functions
Cell membrane
The fundamental structure of the membrane is the phospholipid
bilayer, which forms a stable barrier between two aqueous
compartments. In the case of the plasma membrane, these
compartments are the inside and the outside of the cell.
HISTORY
The sodium-potassium pump was discovered in
1957 by the Danish scientist Jens Christian Skou.
 SodiumpotassiumpumporNa+-K+-ATPaseisanintegral
membraneproteinfoundinthecellsofallhighereukaryotes.
 Itisresponsiblefortranslocatingsodiumandpotassiumions
acrossthecellmembraneutilizingATPasthedrivingforce.
 Thistransportproducesbothachemicalandanelectrical
gradientacrossthecellmembrane.
 Theelectricalgradientisessentialformaintainingtheresting
potentialof cells and forthe excitableactivity of muscleand
nervetissue.
INTRODUCTION
 Thesodiumgradientisusedtodrivenumerous
transportprocesses,includingthetranslocationof
glucose,amino acids,andothernutrientsinto
cells.
 Physiologically,Na+ - K+ ATPasepresent in organs
such as the intestinesand the kidneyregulatesfluid
reabsorption
 It is estimated that approximately23% of the ATP
consumedinhumansatrestisutilizedbythesodium
pump.
Structure
Consists of a catalytic α subunit with ten trans-membrane
segments (8 trans membrane α-helical segments and two large
cytoplasmic inclusions, and - a single trans-membrane
glycosylated β subunit (single trans membrane helix and a large
extracellular domain), required for stabilization.
The α subunit contains the ATPbinding site, the
phosphorylation site, and amino acids essential for the binding
of cations and cardiac glycosides, which suggests that this
subunit plays a major role in the catalytic function of the
enzyme.
The β subunit appears to be involved in maturation of the
enzyme, localization of theATPase to the plasma membrane,
and stabilization of a K+-bound intermediate form of the
protein.
Forms of sodium - potassiumpump
Na+ - K+ATPase exists in two forms-
E1 Form:
E1 has an inward facing high affinity Na+ binding site and
reacts withATPto form the activated product E1~P only when
Na+ is bound.
E2 form :
E2 –P has an outward facing high affinity K+ binding site and
hydrolyses to form P+ E2 only when K+ is bound .
The enzyme, embedded in the phospholipid bilayer, exists in
two main conformations E1 and E2, which are able to
exchange ions at the internal or external side of the membrane,
respectively.
 E2 can be present in a closed, or open, conformation.
MECHANISM
• The pump has a higher affinity for Na⁺ ions than K⁺ ions, thus after
bindingATP, binds 3 intracellular Na⁺ ions.
• ATPis hydrolyzed, leading to phosphorylation of the pump and
subsequent release  dissociate of ADP. This process leads to a
conformational change in the pump.
• The conformational change exposes the Na⁺ ions to the extracellular
region.
• The phosphorylated form of the pump has a low affinity for Na⁺ ions,
so they are released and pushed outside the cell membrane; by
contrast it has high affinity for the K⁺ ions.
• The pump binds 2 extracellular K⁺ ions, which
induces dephosphorylation of the pump, reverting it to its previous
conformational state, thus releasing the K⁺ ions into the cell.
• The unphosphorylated form of the pump has a higher affinity for Na⁺
ions.
• A
TP binds, and the process starts again.
The Electrochemical Gradient
 The active transport of ions across the membrane causes
an electrical gradient to build up across the plasma
membrane.
 The number of positively charged ions outside the cell
is greater than the number of positively charged ions in
the cytosol.
 This results in a relatively negative charge on the inside of
the
 membrane, and a positive charge on the outside.
 This difference in charges causes a voltage across the
membrane
 The voltage across a membrane is called membrane
potential. Membrane potential is very important for the
conduction of electrical impulses along nerve cells.
 Because the inside of the cell is negative compared to
outside the cell, the membrane potential favors the
movement of positively charged ions (cations) into the cell,
and the movement of negative ions (anions) out of the cell.
 So, there are two forces that drive the diffusion of ions across
the plasma membrane a chemical force (the ions'
concentration gradient), and an electrical force (the effect
of the membrane potential on the ions’ movement
electrical gradient).
 These two forces working together are called an
electrochemical gradient.
FUNCTIONS
The job of the sodium-potassium pump is to regulate the
concentration of Na+ and K+ on the inside and outside of the cell.
Na, K-ATPase is important for the overall health of cells. The
pump:
1. Stabilizes the resting membrane potential of cells
2. Produces action potentials
3. Regulates cell volume
4. Help cells such as sperm, neuron, and kidney cells to
perform specialized functions
Resting membrane potential
A neuron at rest is negatively charged,, the inside of a
cell is approximately 70 millivolts more negative than
the outside (−70 mV, note that this number varies by
neuron type and by species). This voltage is called the
resting membrane potential.
 it is caused by differences in the concentrations of ions
inside and outside the cell.
If the membrane were equally permeable to all ions,
each type of ion would flow across the membrane and
the system would reach equilibrium.
The resting membrane potential is a result of different
concentrations inside and outside the cell.
The difference in the number of positively charged
potassium ions (K+) inside and outside the cell dominates
the resting membrane potential
The sodium-potassium pump is responsible for
transporting ions into and out of cells. It contributes to the
maintenance of a cell's resting potential both during and
after stimulation. The cell membrane's potential is
determined by maintaining a low concentration of sodium
and a high concentration of potassium within the cell.
Many secondary active transporters (transport
proteins in the membrane) are activated by Na export
and are responsible for transporting amino acids,
glucose, and other essential nutrients.
The sodium-potassium pump maintains cellular
osmolarity, which regulates cell volume. Osmosis
regulates cell volume. This function maintains and
controls the concentration of various nutrients and
chemical substances.
Other Functions
Sodium and potassium gradients function in various organ
systems' physiologic processes.
The kidneys have a high level of expression of the Na, K-
ATPase, with the distal convoluted tubule expressing up to 50
million pumps per cell. This sodium gradient is necessary for
the kidney to filter waste products in the blood, reabsorb
amino acids, reabsorb glucose, regulate electrolyte levels in the
blood, and to maintain pH.
Sperm cells also use the Na, K-ATPase, but they use a different
isoform necessary for preserving fertility in males. Sperm needs
the Na, KATPase to regulate membrane potential and ions,
which is necessary for sperm motility and the sperm’s
acrosome functioning during penetration into the egg.
Na-K Pump Maintains Cell Resting Potential

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Na-K Pump Maintains Cell Resting Potential

  • 1. Presented by: Husna zaheer MS Inorganic chemistry Lahore College for Women University
  • 3. Contents: History Introduction Structure Forms of sodium - potassium pump Mechanism The Electrochemical Gradient Functions
  • 4. Cell membrane The fundamental structure of the membrane is the phospholipid bilayer, which forms a stable barrier between two aqueous compartments. In the case of the plasma membrane, these compartments are the inside and the outside of the cell.
  • 5. HISTORY The sodium-potassium pump was discovered in 1957 by the Danish scientist Jens Christian Skou.
  • 6.  SodiumpotassiumpumporNa+-K+-ATPaseisanintegral membraneproteinfoundinthecellsofallhighereukaryotes.  Itisresponsiblefortranslocatingsodiumandpotassiumions acrossthecellmembraneutilizingATPasthedrivingforce.  Thistransportproducesbothachemicalandanelectrical gradientacrossthecellmembrane.  Theelectricalgradientisessentialformaintainingtheresting potentialof cells and forthe excitableactivity of muscleand nervetissue. INTRODUCTION
  • 7.  Thesodiumgradientisusedtodrivenumerous transportprocesses,includingthetranslocationof glucose,amino acids,andothernutrientsinto cells.  Physiologically,Na+ - K+ ATPasepresent in organs such as the intestinesand the kidneyregulatesfluid reabsorption  It is estimated that approximately23% of the ATP consumedinhumansatrestisutilizedbythesodium pump.
  • 8. Structure Consists of a catalytic α subunit with ten trans-membrane segments (8 trans membrane α-helical segments and two large cytoplasmic inclusions, and - a single trans-membrane glycosylated β subunit (single trans membrane helix and a large extracellular domain), required for stabilization. The α subunit contains the ATPbinding site, the phosphorylation site, and amino acids essential for the binding of cations and cardiac glycosides, which suggests that this subunit plays a major role in the catalytic function of the enzyme. The β subunit appears to be involved in maturation of the enzyme, localization of theATPase to the plasma membrane, and stabilization of a K+-bound intermediate form of the protein.
  • 9.
  • 10. Forms of sodium - potassiumpump Na+ - K+ATPase exists in two forms- E1 Form: E1 has an inward facing high affinity Na+ binding site and reacts withATPto form the activated product E1~P only when Na+ is bound. E2 form : E2 –P has an outward facing high affinity K+ binding site and hydrolyses to form P+ E2 only when K+ is bound . The enzyme, embedded in the phospholipid bilayer, exists in two main conformations E1 and E2, which are able to exchange ions at the internal or external side of the membrane, respectively.  E2 can be present in a closed, or open, conformation.
  • 11.
  • 12. MECHANISM • The pump has a higher affinity for Na⁺ ions than K⁺ ions, thus after bindingATP, binds 3 intracellular Na⁺ ions. • ATPis hydrolyzed, leading to phosphorylation of the pump and subsequent release dissociate of ADP. This process leads to a conformational change in the pump. • The conformational change exposes the Na⁺ ions to the extracellular region. • The phosphorylated form of the pump has a low affinity for Na⁺ ions, so they are released and pushed outside the cell membrane; by contrast it has high affinity for the K⁺ ions. • The pump binds 2 extracellular K⁺ ions, which induces dephosphorylation of the pump, reverting it to its previous conformational state, thus releasing the K⁺ ions into the cell. • The unphosphorylated form of the pump has a higher affinity for Na⁺ ions. • A TP binds, and the process starts again.
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  • 14. The Electrochemical Gradient  The active transport of ions across the membrane causes an electrical gradient to build up across the plasma membrane.  The number of positively charged ions outside the cell is greater than the number of positively charged ions in the cytosol.  This results in a relatively negative charge on the inside of the  membrane, and a positive charge on the outside.  This difference in charges causes a voltage across the membrane  The voltage across a membrane is called membrane potential. Membrane potential is very important for the conduction of electrical impulses along nerve cells.
  • 15.  Because the inside of the cell is negative compared to outside the cell, the membrane potential favors the movement of positively charged ions (cations) into the cell, and the movement of negative ions (anions) out of the cell.  So, there are two forces that drive the diffusion of ions across the plasma membrane a chemical force (the ions' concentration gradient), and an electrical force (the effect of the membrane potential on the ions’ movement electrical gradient).  These two forces working together are called an electrochemical gradient.
  • 16. FUNCTIONS The job of the sodium-potassium pump is to regulate the concentration of Na+ and K+ on the inside and outside of the cell. Na, K-ATPase is important for the overall health of cells. The pump: 1. Stabilizes the resting membrane potential of cells 2. Produces action potentials 3. Regulates cell volume 4. Help cells such as sperm, neuron, and kidney cells to perform specialized functions
  • 17. Resting membrane potential A neuron at rest is negatively charged,, the inside of a cell is approximately 70 millivolts more negative than the outside (−70 mV, note that this number varies by neuron type and by species). This voltage is called the resting membrane potential.  it is caused by differences in the concentrations of ions inside and outside the cell. If the membrane were equally permeable to all ions, each type of ion would flow across the membrane and the system would reach equilibrium.
  • 18. The resting membrane potential is a result of different concentrations inside and outside the cell. The difference in the number of positively charged potassium ions (K+) inside and outside the cell dominates the resting membrane potential The sodium-potassium pump is responsible for transporting ions into and out of cells. It contributes to the maintenance of a cell's resting potential both during and after stimulation. The cell membrane's potential is determined by maintaining a low concentration of sodium and a high concentration of potassium within the cell.
  • 19. Many secondary active transporters (transport proteins in the membrane) are activated by Na export and are responsible for transporting amino acids, glucose, and other essential nutrients. The sodium-potassium pump maintains cellular osmolarity, which regulates cell volume. Osmosis regulates cell volume. This function maintains and controls the concentration of various nutrients and chemical substances. Other Functions
  • 20. Sodium and potassium gradients function in various organ systems' physiologic processes. The kidneys have a high level of expression of the Na, K- ATPase, with the distal convoluted tubule expressing up to 50 million pumps per cell. This sodium gradient is necessary for the kidney to filter waste products in the blood, reabsorb amino acids, reabsorb glucose, regulate electrolyte levels in the blood, and to maintain pH. Sperm cells also use the Na, K-ATPase, but they use a different isoform necessary for preserving fertility in males. Sperm needs the Na, KATPase to regulate membrane potential and ions, which is necessary for sperm motility and the sperm’s acrosome functioning during penetration into the egg.