Sodium potassium pump
- 1. SODIUM-POTASSIUM PUMP {Sem-5,Paper-2, Unit-4} Abhijeet Bhattacharya KSD’s Model College Dombivali
- 2. Introduction ➢Sodium-Potassium Pump or Na+ -K+ -ATPase is an integral membrane protein found in the cells of all higher eukaryotes. ➢It is responsible for translocating sodium and potassium ions across the cell membrane utilizing ATP as the driving force
- 3. Introduction ➢For every three sodium ions pumped out of the cell, two potassium ions are pumped in. ➢This transport produces both a chemical and an electrical gradient across the cell membrane. ➢The electrical gradient is essential for maintaining the resting potential of cells and for the excitable activity of muscle and nerve tissue. ➢The sodium gradient is used to drive numerous transport processes, including the translocation of glucose, amino acids, and other nutrients into cells.
- 4. Introduction ➢Physiologically, Na+ - K + ATPase present in organs such as the intestines and the kidney regulates fluid reabsorption and electrolyte movement by establishing an ionic gradient across epithelial membranes. ➢It is estimated that approximately 23% of the ATP consumed in humans at rest is utilized by the sodium pump. ➢The Na+--K+ -ATPase is a member of the P-type class of active cation transport proteins of ATPases
- 5. History ➢The sodium-potassium pump was discovered in 1957 by the Danish scientist Jens Christian Skou. ➢He was awarded a Nobel Prize for his work in 1997.
- 6. Structure ➢The Na+ - K + -ATPase can function as an α β dimer. ➢There are four isoforms of α(1- 4) and three isoforms of β expressed in a tissue-specific fashion.
- 7. Structure ➢The α subunit contains the ATP binding site, the phosphorylation site, and amino acids essential for the binding of cations and cardiac glycosides. ➢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 the ATPase to the plasma membrane, and stabilization of a K + -bound intermediate form of the protein.
- 8. Electrogenic pump ➢Drives 3 positively charged ions (Na+ ) out of the cell for every 2 it pumps in (K+ ). ➢It drives a net electrical charge across the membrane ,tending to create an electrical potential, with cell’s inside being negative relative to outside. ➢This electrogenic effect of the pump, how ever seldom directly contributes more than 10% of the membrane potential.
- 9. Forms of sodium - potassium pump ➢Na+ - K + ATPase exists in two forms- ➢E1 Form: E1 has an inward –facing high affinity Na+ binding site and reacts with ATP to 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 Pi + E2, only when K+ is bound .
- 10. Mechanism The (Na+ -K + )-ATPase operates in accordance with the following ordered sequential reaction scheme: 1)E1: 3Na+ ,which acquired its Na+ inside the cell, binds ATP to yield the tertiary complex E1 .ATP.Na+ 2)The tertiary complex reacts to form the high energy aspartyl phosphate intermediate E1~P.3Na+ 3)This high energy intermediate relaxes to its low energy conformation ,E2 -P.3Na+ and relaxes its bound sodium outside the cell
- 11. 4)E2 -P binds 2K+ from outside the cell to form E2 -P.2k+ . 5) The phosphate group is hydrolyzed, yielding E2 .2K+ 6) E2 .2K+ changes conformation, releases its 2K+ inside the cell ,and replaces its Na+ , thereby completing the transport cycle.
- 12. INHIBITION ➢The pump requires binding by Na+ , K+ and ATP for its operation. Therefore , if the concentration of any of these substances is too low , the pump does not function. ➢When the temperature is reduced. ➢During oxygen lack. ➢Metabolic Poisons e.g. 2,4 DNP that prevents the formation of ATP.
- 13. Function Resting Potential ➢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 sodium-potassium pump mechanism moves 3 sodium ions out and moves 2 potassium ions in. ➢Thus, in total removing one positive charge carrier from the intracellular space
- 14. Function Transport Export of sodium from the cell provides the driving force for several secondary active transporters' membrane transport proteins, which import glucose, amino acids, and other nutrients into the cell by use of the sodium gradient.
- 15. Function Controlling Cell Volume ➢Failure of the Na+ -K +pumps can result in swelling of the cell. ➢A cell's osmolarity is the sum of the concentrations of the various ion species and many proteins and other organic compounds inside the cell. ➢When this is higher than the osmolarity outside of the cell, water flows into the cell through osmosis. This can cause the cell to swell up and lyse. ➢The Na+ -K +pump helps to maintain the right concentrations of ions. Furthermore, when the cell begins to swell, this automatically activates the Na+ -K + pump.
- 16. Function Controlling Neuron activity. ➢The Na+ -K + pump has been shown to control and set the intrinsic activity mode of cerebellar Purkinje neurons, accessory olfactory bulb mitral cells and probably other neuron types. ➢ Pump not simply be a homeostatic molecule for ionic gradients; but could be a computation element in the cerebellum and the brain . ➢Mutation in the Na+ -K + pump causes rapid onset dystonia parkinsonism.