Active Transport and the Sodium Pump Lecture Flashcards
07/11/24
What is the sodium pump?
An integral membrane protein, which is an enzyme capable of the vectorial transport of Na+ and K+ across the membrane. Na+ is extruded against its concentration gradient.
What is the structure of the sodium pump?
2 transmembrane α-subunits and 2 surface level β-subunits. ATP binding sites on the intracellular surface of the α-subunits and cardiac glycoside binding sites on the extracellular surface.
What are prominent features of the sodium pump?
ATP must be available intracellularly
Na+ ions bind internally (3)
K+ ions bind externally (2)
Most cells have approx. 1 million Na+ pump sites.
Cardiac glycosides only inhibit on the extracellular surface.
What is the sodium pump equation?
[3Na+]i + [2K+]o ⇌ [3Na+]o + [2K+]i
Reaction with the use of ATP used in ATP hydrolysis to release energy, catalysed by ATPase(hydrolase).
What is Km?
The concentration of substrate that permits the enzyme to achieve half of Vmax. i.e. an enzyme with a high Km has a low affinity for its substrate and requires a greater conc. of substrate to achieve Vmax.
What affects the sodium pump?
The reaction occurs 100 times per second.
Can be inhibited by removing [K+]o
Can be stimulated by increasing [Na+]i
What can be used to inhibit the sodium pump?
Cardiac glycosides, or digoxin, can be used to inhibit the sodium pump. It is used as a treatment for heart failure and arrhythmias.
How does digoxin work?
It works by blocking the Na+/K+ pump - so higher intracellular Na+, and therefore more of an influx of Ca2+ in the heart, which causes an increase and contractility.
How can the concentration of K+ affect digoxin?
Artificially increasing or decreasing [K+]o will change the way digoxin affects the sodium pump. An increase in [K+]o will lead to a shift of the curve to the right, meaning digoxin is less effective.
What is the therapeutic index?
Minimum effective dose for 50% of the population (ED50).
What is hypokalaemia?
Low blood potassium concentrations - less than 3.5 mEq/L. Symptoms include abnormal heart rhythms, muscle damage, paralysis.
What is hyperkalaemia?
High blood potassium concentrations - more than 5.5. Symptoms include nausea, palpitations and muscle weakness.
What is the relationship between digoxin and hypokalaemia?
Digoxin toxicity is heightened by hypokalaemia, and hyperkalaemia diminishes digoxin’s effectiveness.
How is ATPase activated?
When 2x K+ are bound to the external sites and 3x Na+ to the internal sites ATPase is activated.
Describe intestinal uptake of glucose: SGLT1
Sodium diffuses into the bloodstream from the epithelial cells in the gut which creates a concentration gradient between the epithelial cell and the lumen of the intestine. Sodium ions then move into the epithelial through a symporter protein, but they are also coupled up with a glucose molecule, so while sodium is travelling down the concentration gradient, glucose is travelling against its own. Glucose can then be absorbed into the bloodstream by facilitated diffusion.
