The sodium potassium pump It is a protein structure included in a broader set of molecules present in many cell membranes, and which are responsible for the active transport of ions or other small molecules against their concentration gradients. They use the energy released by the hydrolysis of ATP and that is why they are generically called ATPases.
The sodium potassium pump is a Na + / K + ATPase because it releases the energy contained in the ATP molecule to move sodium from the inside to the outside of the cell, while introducing potassium.
Inside the cell, sodium is less concentrated (12 mEq / L) than outside (142 mEq / L), while potassium is more concentrated outside (4 mEq / L) than inside (140 mEq / L).
ATPase pumps are classified into three large groups:
Sodium potassium pumps (Na + / K + ATPase) belong to the group of P-class ion pumps and were discovered in 1957 by Jens Skou, a Danish researcher, when he was studying the mechanism of action of anesthetics on the nerves of a crab (Carcinus maenas); work for which he was awarded the Nobel Prize in Chemistry in 1997.
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The sodium potassium pump is an enzyme that from the point of view of its quaternary structure is formed by 2 protein subunits of the alpha (α) type and two of the beta (β) type.
It is, therefore, a tetramer of the α2β2 type, whose subunits are integral membrane proteins, that is, they cross the lipid bilayer and have both intra- and extra-cytosolic domains..
The α subunits are those that contain the binding sites for ATP and for the Na + and K + ions and represent the catalytic component of the enzyme and the one that exerts the function of the pump itself..
The α subunits are large polypeptides, with a molecular weight of 120 kDa, 10 transmembrane segments and with their N- and C-terminal ends located on the cytosolic side..
They have binding sites for ATP and Na + on the intracellular side, as well as an aspartate residue at position 376 that represents the site that undergoes the phosphorylation process during pump activation..
The binding site for K + appears to be on the extracellular side.
The β subunits do not seem to have a direct participation in the pumping function, but in their absence this function does not occur..
The β subunits have a molecular weight of about 55 kDa each and are glycoproteins with a single transmembrane domain whose carbohydrate residues are inserted in the extracellular region..
They seem to be necessary in the endoplasmic reticulum, where they would contribute to the proper folding of the α subunits, and then, at the membrane level, to stabilize the complex..
Both types of subunits are heterogeneous and α1, α2 and α3 isoforms have been described for one, and β1, β2 and β3 for the other. Α1 is found in the membranes of most cells, while α2 is present in muscle, heart, adipose tissue and brain and α3 in heart and brain.
The β1 isoform is the one with the most diffuse distribution, although it is absent in some tissues such as the vestibular cells of the inner ear and the rapidly responding glycolytic muscle cells. The latter contain only β2.
The different structures of the subunits that make up the Na + / K + pump in the different tissues may be due to functional specializations that have not yet been elucidated..
For any moment considered, the plasma membrane constitutes a separation boundary between the compartment corresponding to the interior of a cell and that which represents the extracellular fluid in which it is immersed..
Both compartments have a composition that can be qualitatively different, since inside cells there are substances that are not found outside of them and the extracellular fluid contains substances that are not present intracellularly..
Substances that are present in both compartments can be found in different concentrations, and these differences can have physiological significance. Such is the case with many ions.
The Na + / K + pump plays a fundamental role in maintaining intracellular homeostasis by controlling the concentrations of sodium and potassium ions. This maintenance of homeostasis is achieved thanks to:
Na + has an extracellular concentration of about 142 mEq / L, while its intracellular concentration is only 12 mEq / L; K +, on the other hand, is more concentrated inside the cell (140 mEq / L) than outside it (4 mEq / L).
Although the electric charge of these ions does not allow their passage through the membrane, there are ion channels that do allow it (selectively), which promote movement if the forces that ordinarily move these ions are also present..
Now these differences in concentration are of great importance in the preservation of homeostasis of the organism and must be maintained in a kind of balance that if lost would produce important organic alterations.
The function of the Na + / K + pump allows the extraction of sodium that has entered by diffusion through channels or other transport routes and the reintroduction of potassium that has diffused out, allowing the conservation of intra and extracellular concentrations of these ions.
The mechanism of action of the ATPase Na + / K + consists of a catalytic cycle that involves transfer reactions of a phosphoryl group (Pi) and conformational changes of the enzyme that goes from an E1 state to an E2 state and vice versa..
The operation requires the presence of ATP and Na + inside the cell and K + in the extracellular fluid.
The cycle begins in the E1 conformation state of the enzyme, in which there are 3 cytosolic sites of binding to Na + and high affinity (Km of 0.6 mM) that are fully occupied because the intra-ion concentration ( 12 mM) allows it.
In this state (E1) and with Na + attached to its binding sites, ATP binds to its site in the cytosolic sector of the molecule, hydrolyzes and a phosphate group is transferred to aspartate 376, forming a high-energy acylphosphate that induces a conformational change to state E2.
The conformational change to the E2 state implies that the Na + binding sites pass to the outside, their affinity for the ion decreases greatly and it is released into the extracellular fluid, while, at the same time, the affinity of the K + binding sites increases. and these ions are attached to the outside of the pump.
Once the Na + is released and the K + is bound, the hydrolysis of aspartyl phosphate occurs and the conformational change from the E2 state to the E1 state is reverted, with the reintroduction of the empty Na + binding sites and those of occupied K +.
When this change occurs, the sites for Na + regain their affinity and those for K + lose it, with which the K + is released into the cell..
The Na + / K + pump is present in most, if not all, mammalian cells, in which it is of general importance by helping to maintain their osmolarity and therefore their volume.
The continuous entry of sodium ions into the cell leads to an increase in the intracellular number of osmotically active particles, which induces the entry of water and the increase in volume that would end up causing the rupture of the membrane and cell collapse..
As these pumps introduce only 2 K + for every 3 Na + they remove, they behave electrogenically, which means that they "decompensate" the internal electrical charges, favoring the production of the membrane potential characteristic of body cells..
Its importance is also evident in relation to the cells that make up excitable tissues, in which the action potentials are characterized by the entry of the Na + ion, which depolarizes the cell, and the exit of K +, which repolarizes it..
These ionic movements are possible thanks to the operation of the Na + / K + pumps, which contribute to the production of the chemical gradients that move the ions involved..
Without these pumps, operating in the opposite direction, the concentration gradients of these ions would dissipate and the excitatory activity would disappear..
Another aspect that highlights the extreme importance of sodium-potassium pumps is related to kidney function, which would be impossible without them.
Kidney function involves the daily filtration of more or less 180 liters of plasma and large amounts of substances, some of which must be excreted, but many have to be reabsorbed so that they are not lost through the urine..
The reabsorption of sodium, water and many of the filtered substances depends on these pumps, which are located in the basolateral membrane of the cells that make up the epithelia of the different tubular segments of the kidney nephrons..
The epithelial cells that line the renal tubules have one side that is in contact with the lumen of the tubule and is called the apical side, and another that is in contact with the interstitium around the tubule and called the basolateral side..
Water and reabsorbed substances must first pass into the cell through the apical and then into the interstitium through the basolateral.
The reabsorption of Na + is key both in relation to it, and in relation to that of water and that of other substances that depend on it. The apical entry of Na + into the cell requires that there be a gradient that moves it and that implies a very low concentration of the ion inside the cell..
This low intracellular concentration of Na + is produced by the sodium pumps of the basolateral membrane that work intensively to remove the ion from the cells into the interstitium..
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