Function

The primary function of this protein serves as the catalytic component of the active enzymes, which catalyzes the hydrolysis of the ATP coupled with the exchange of sodium and potassium across the plasma membrane. Additionally, this action potential assists in creating an electrochemical gradient of sodium and potassium ions by delivering the energy for the active transport of numerous nutrients.^[1] Therefore, the NA+/K+ pump functions by having to transport sodium and potassium ions across the cell membrane in a 3 to 2 ratio (3 Na+ out and 2 K+ in). By doing this, the membrane potential increases its stability and therefore is essential in human cells as it constantly maintains an optimal ion balance.^[2] In addition, the sodium-potassium pump functions in many systems. A high level of expression can be found in the kidneys as they are responsible for expressing 50 million pumps per cell to filter waste products in the blood, maintain optimal pH's, regulate electrolyte levels, and reabsorb glucose and amino acids. Another important place this ATPase activity can be seen is in the brain as the neurons need this pump to reverse postsynaptic sodium flux to activate action potentials.^[3]

Disease

If the Sodium Potassium Pump stops working or is inhibited, the sodium concentration will add up within the cell, and the intracellular potassium levels will fall. This has been shown to cause reduced intelligence, loss of Magnesium in urine, and epileptic seizures. This happens due to a mutation in the Alpha 1 form of the Sodium Potassium Pump. It is shown that the mutated protein is found both in the kidneys and the brain. Epileptic seizures occur because the kidneys, instead of absorbing the Magnesium, will secrete it in the urine caused by the convolutions of the protein itself.^[4] This has been shown to lead to mental retardation in some cases. Additionally, the overarching picture of the sodium-potassium pump deficiency can cause severe damages. In short, the nervous and the muscular system will shut down so quickly; one would experience paralysis, interruption of heartbeat and respiration, and cessation of all brain and nerve activity. This would cause the nervous system to be non-functional and ultimately result in death.^[5]

Relevance

The Sodium Potassium Pump is relevant because it creates an action potential throughout the cell membrane. This results in an imbalance of ions, which causes displacement between the outside and inside the cell. Physiologically speaking, this is why our nerve cells can propagate signals throughout the human body.^[6] This protein is vital to our daily function as this Na+/K+ ATPase uses fifteen percent of our caloric intake in one day. The pump is also relevant to glucose absorption as that is crucial in human metabolism. This starts with Na+ ions being pumped out of cells in the small intestine into the blood with the help of the Sodium Potassium Pump. The Sodium-ion will later re-enter the small intestine cells via diffusion through a Sodium-Glucose Transporter Protein (SGLUT-1). This will cause the glucose concentration inside the cell to increase and form a gradient between inside the cell and the blood. This will assist glucose into the blood via facilitated diffusion.^[7] Finally, both Na+ and K+ are found in the body as a form of electrolytes. Potassium assists in making various proteins, anabolism of carbohydrates in tissues, and helps support the electrical activity in the heart. Whereas sodium assists in maintaining healthy fluid balance, contractions of muscle, and conduction of nerve impulses. Avoiding this naturally occurring phenomenon can inhibit mental and physical growth.^[8]

Structural highlights

The Sodium Potassium Pump is a transmembrane protein that consists of the alpha, beta, and FXYD Subunits. The alpha subunit consists of The actuator domain (A), the nucleotide-binding domain (N), and the phosphorylation domain (P). These domains function in the rate of ion transports and signaling. The Beta subunit consists of a few gatherings of . This is very crucial as this helps target the polypeptide to the membrane and overall improved stability.^[9] Additionally, the Na+ K+ pump alternates between two conformations: E1 and E2. In the , the ATP will be cleaved and the gamma phosphate will be moved to ASP376. The phosphate group is shown by an MgF4 Analog. In the , the site of binding consists of THR779, SER782, ASN783, and ASP811. These function in creating a kink so that the K+ ion can bind to this site.^[10]