L: Active Transport and the sodium potassium pump

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Is there more sodium inside the cell or outside the cell?

Outside the cell.

Is there more potassium inside the cell or outside the cell.

Inside the cell.

What is the sodium potassium pump also known as?

Na⁺/K⁺ ATPase.

What type of molecule is the sodium potassium pump?

An enzyme - protein.

What is the sodium pump?

An active transport system that moves sodium ions out of the cell.

What is the structure of the sodium potassium pump?

2 alpha subunits in the middle that extend all the way through the membrane, and 2 beta subunits that are on the outside near the extracellular surface.

What is a tetramer?

A molecule composed of 4 subunits.

What is the approximate molecular weight of the sodium potassium pump?

274,000 - 280,000 

Where does ATP bind?

Intracellularly.

Where do sodium ions bind?

Internally and 3 at the alpha subunit.

Where do potassium ions bind?

Externally and 2 at the alpha subunit.

Approximately how many sodium pump sites do most cells have?

1 million.

What happens to ATP during the sodium pump?

It is hydrolysed to ADP.

What is Km?

The concentration of substrate which allows an enzyme to reach half of Vmax.

What does a high Km mean for the enzyme?

That it has a low affinity for the substrate and requires a greater concentration of substrate to achieve Vmax.

What is the Km for sodium?

20mM.

What is the Km for potassium?

1mM.

What is the rate limiting factor for the sodium potassium pump?

The intracellular sodium ion concentration, as there is usually only about 10mM inside the cell.

How many times a second does the reaction occur?

100 times.

What could be removed to inhibit the reaction?

Extracellular potassium.

What could be added to stimulate the reaction?

Increasing intracellular sodium.

What is digoxin used to treat?

Heart failures and arrhythmias.

What does digoxin do?

It blocks the Na+/K+ pump which induces an increase in intracellular Na+, this will drive an influx of calcium in the heart and cause an increase in contractility.

Why would there be increased binding between cardiac glycosides and the sodium pump?

A decrease in extracellular potassium.

What is hypokalaemia?

Low potassium levels in the blood.

What would hypokalaemia result in for digoxin?

Increased digoxin binding.

Which surface do cardiac glycosides inhibit from?

The extracellular surface.

What is the calculation for therapeutic index?

Dose producing toxicity in 50% of the population / minimum dose effective for 50% of the population.

What is the therapeutic index of digoxin?

2:1.

What is the range for hypokalaemia?

Less than 3.5.

what is the range for moderate hypokalaemia?

3.0-2.5

What is the range for severe hypokalaemia?

Less than 2.5.

What are the symptoms of hypokalaemia?

• Abnormal heart rhythms

• Muscle damage (rhabdomyolysis)

• muscle weakness or spasms

• paralysis

What is the range for normokalaemia?

3.6 - 5.2

What is the range for hyperkalaemia?

More than 5.5

what is the range for moderate hyperkalaemia?

6.1-6.9

What is the range for sever hyperkalaemia?

More than 7.0

What are the symptoms of hyperkalaemia.

• Nausea

• Palpitations

• Muscle weakness

• Over approx. 7.0 → cardiac arrest

What heightens digoxin toxicity?

Hypokalaemia.

Where does digoxin bind?

The K+ site of the Na+/K+ APTase.

What dimities digoxin’s effectiveness?

Hyperkalaemia.

What does primary transport mean for ATP?

It directly couples the hydrolysis of ATP to molecular movement.

What energy does does secondary transport use?

Stored energy to drive molecular transport against the electrochemical gradient.

What is the function of the sodium potassium pump?

It transports Na+ out of cells and K+ into cells

Maintains the Na+ and K+ difference across cell membranes

Establishes a negative voltage inside the cell (relative to outside) which is vital for nerve function and signal transmission.

What is the molecular weight of the beta subunit?

40,000 mW.

What is the function of the beta subunit?

Its function is not clear.

What is the molecular weight of the alpha subunit?

100,000 mW.

What does the alpha subunit bind to?

ATP, 3 Na+ and 2 K+

Where does ATPase activity happen?

On the internal side near the Na+ binding sites.

What activates ATP?

When 2 K+ and 3 Na+ bind to the sodium potassium pump.

What is 1 ATP cleaved into?

ADP and a high energy phosphate.

What causes Na to be moved out of the cell and potassium to be moved into the cell?

Phosphorylation - it causes a chemical and conformational change to the carrier protein.

What determines the direction of the pump?

Na+, K+, ATP and ADP concentrations.

What is the sodium potassium pump important for controlling?

Cell volume.

What contributes to the electrical potential across the membrane?

The net loss of ions (3 out, 2 in per pump action).

In electrically active nerve cells, what percentage of the cells ATP is used to pump sodium and potassium?

60-70%.

What would happen if sodium was not pumped out of the cell?

The cell would burst.

What does the net transfer of ions out of the cell prevent?

Water being pulled into the cell due to osmotic pressure.

What is the sodium calcium exchanger?

A secondary active transport counter (antiport) transport.

What are the glucose transporters?

GLUT 1,2,3,4 and 5

What does GLUT 1.

Basal uptake in placenta and brain.

What does GLUT 2 do?

transepithelial transport and B cells.

What does GLUT 3?

Basal uptake in brain.

Where is GLUT 4 ?

In skeletal muscle (insulin dependent)

What does GLUT 5 do?

Intestinal absorption of fructose.

What transporter does intestinal uptake of glucose use?

Sodium dependant glucose transporter 1. (SGLT 1)

What is the other isoform of Na+ dependant glucose transporter?

SGLT 2

What has a higher Km SGLT 1 or 2?

SGLT 2 (1.6), as SGLT 1 has a Km of 0.8.

Why has a higher affinity for its substrate SGLT 1 or 2?

SGLT 1.

What is the sodium to glucose ratio for SGLT 1?

2:1

What is the accumulation ratio of SGLT 1?

30,000:1

What type of transport is Na+ dependant glucose transport?

Secondary active co-transport.

What is the sodium to glucose ratio for SGLT 2?

1:1

What is the accumulation ratio for SGLT 2?

200:1

What type of transport does transepithelial glucose transport use?

GLUT 2 facilitated diffusion.

What is the function of diuretics?

They increase urine output by the kidneys, they promote diuresis.

What are diuretics used as treatment for?

High blood pressure and excessive fluid retention.

What are the side effects of diuretics?

Loop diuretics increase the urinary excretion of potassium.

What is an example of a loop diuretic?

Furosemide.

What may happen to patients who start diuretics?

They may become hypokalaemic.

Why is it so easy for patients to develop digoxin toxicity?

Digoxin has a very narrow therapeutic index.

What is the treatment for digoxin toxicity?

Administer a digoxin binding antibody.

What does digibind do?

Rapidly binds to the digoxin, causing it to dissociate from the sodium pump, reversing the toxicity associated with the increased sodium pump inhibition.