Active transport Flashcards

1
Q

Describe the structure and function of the sodium pump

A

The sodium pump is an integral membrane protein which is an enzyme capable of the vectorial transport of Na+ and K+ across the membrane.

The sodium pump has alpha and beta subunits.

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2
Q

Features of the sodium potassium pump

A

The sodium/potassium pump is an Alpha2Beta2 tetramer, MW 270000

Na+ ions bind internally (3 per alpha)
K+ ions bind externally (2 per alpha)

ATP binding sites are intracellular

Most cells have approximately 1 million sodium pump sites.

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3
Q

Where are the ATP binding sites ?

A

Found intracellularly

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4
Q

Where are the cardiac glycoside binding sites ?

A

Found extracellularly
They ONLY inhibit from the extracellular surface

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5
Q

Sodium pump equation

A

3[Na+]i + 2[K+]o <=> 3[Na+]o + 2[K+]I

ATP is hydrolysed to ADP by the enzyme (Na+ + K+)ATPase

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6
Q

Molecular weight of alpha and beta

A

Alpha - 95000
Beta - 40000

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7
Q

Sodium and Potassium concentrations inside and outside

A

OUTSIDE
Na+ : 140mM
K+ : 5mM

INSIDE
Na+ : 10mM
K+ : 140mM

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8
Q

How do cells maintain their steady-state intracellular ionic concentrations ?

A

Passive diffusion :
Na into the cell
K out of the cell

Active transport
3 Na out of the cell
2 K into the cell

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9
Q

Km

A

The concentration of substrate which permits the enzyme to achieve 1/2 Vmax.

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10
Q

Describe an enzyme with a High Km

A

An enzyme with a high Km has a low affinity for its substrate and requires a greater concentration of substrate to achieve Vmax.

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11
Q

What is the rate limiting factor in the sodium pump ?

A

So, intracellular sodium ion conc is rate limiting factor (in normal physiological situation) as usually only about 10mM inside the cell

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12
Q

How can the sodium potassium pump be inhibited and stimulated ?

A

Inhibited by removing [K+]o
Stimulated by increasing [Na+]i

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13
Q

How many times does the sodium potassium pump reaction occur per second ?

A

100 times per second

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14
Q

Cardiac Glycosides

A

Digoxin

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15
Q

Uses of digoxin

A

Used to treat heart failure and arrhythmias

Blocks the Na/K pump

Induces increase in intracellular Na+ that will drive an influx of calcium in the heart and cause an increase in contractility.

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16
Q

What does a decrease in [K+]o result in ?

A

Increased binding between cardiac glycosides and the sodium pump.

Decreased [K+]o leads to increased digoxin binding.

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17
Q

Hypokalaemia

A

Low blood potassium levels

RANGE : Less than 3.5

Moderate : 2.5-3.0
Severe : less than 2.5

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18
Q

Symptoms of hypokalaemia

A

Abnormal heart rhythms
Muscle damage
Muscle weakness / spasms
Paralysis

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19
Q

Norokalaemia

A

Normal blood potassium levels

RANGE : 3.6-5.2

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20
Q

Hyperkalaemia

A

High blood potassium levels

RANGE : More than 5.5

Moderate : 6.1-6.9
Severe : more than 7.0

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21
Q

Symptoms of hyperkalaemia

A

Nausea
Palpitations
Muscle weakness

Over approx 7.0, cardiac arrest

22
Q

How is digoxin toxicity hightened ?

A

By hypokalaemia

As digoxin ends to the K+ site of the Na+/K+ ATPase pump, low serum potassium levels increase the risk of digoxin toxicity.

23
Q

Digoxin feature

A

Has a very narrow therapeutic index

24
Q

Results of hyperkalaemia

A

It diminishes digoxins effectiveness

25
Q

Briefly explain the clinical significance of the interaction between the binding of the cardiac glycosides and the extracellular potassium concentration.

A

Increased binding between cardiac glycosides and the sodium pump as a result of the decrease in [K+]o.

This results in increased digoxin binding, which blocks the Na/K ATPase pump.

Induces increase in intracellular Na+ that will drive an influx of calcium in the heart and cause an increase in contractility.

(Used to treat heart failure and arrhythmias)

26
Q

Therapeutic index

A

The minimum effective dose for 50% of the population

27
Q

Values of therapeutic index

A

More than ED50
Less than TD50

28
Q

Use of digoxin and therapeutic index

A

Congestive heart failure

2:1

29
Q

Use of remifentanil and therapeutic index

A

Patient controlled analgesia (pain relief) during labour
Synthetic opioid

33000:1

30
Q

Use of diazepam and therapeutic index

A

Sedative

100:1

31
Q

Use of ethanol and therapeutic index

A

Sedative

10:1

32
Q

Explain the difference between primary and secondary active transport

A

Primary directly couples the hydrolysis of ATP to molecular movement.

Secondary uses stored energy

e.g. in the Na+ gradient (generated by the sodium pump) to drive molecular transport against the electrochemical gradient.

33
Q

Sodium - potassium pump

A

Transports Na+ out of the cells and K+ into cells

Maintains the Na+ and K+ differences across cell membranes

Establishes a negative voltage inside the cell (compared with outside) vital for nerve function and signal transduction.

34
Q

Importance of negative voltage inside the cell generated by the sodium-potassium pump

A

It is vital for nerve function and signal transduction

35
Q

Describe the sodium potassium pump activation

A

When 2 x K+ are bound to the external K+ sites and 3 x Na+ to the internal sites ATPase is activated.

One ATP is cleaved to ADP + 1 x high energy phosphate bond (Pi)

Phosphorylation causes a chemical and conformational change to the carrier protein causing the 3 x Na+ to be extruded across the membrane and the 2 x K+ to be introduced into the cell.

36
Q

Role of the sodium/potassium pump

A

Maintains cell volume

The membrane is not very permeable to Na+ but a small amount does leak through.

Na+ must be pumped out of the cell or it would eventually burst.

37
Q

Results of net transfer of ions out of the cell

A

a) Dilutes the cytosol

b) Without this, (too much) water would be pulled into the cell due to osmotic pressure (due to high conc. of osmotically active Na+) and the cell would burst.

38
Q

GLUT1

A

Basal uptake in placenta and brain

39
Q

GLUT2

A

Transepithelial transport, Beta cells

40
Q

GLUT3

A

Basal uptake in the brain

41
Q

GLUT4

A

Skeletal muscle (insulin dependent)

42
Q

GLUT5

A

Intestinal absorption of fructose

43
Q

Na+ dependent glucose transporter isoforms

A

SGLT1
SGLT2

44
Q

SGLT1

A

Km - 0.8
Affinity - High
Na+/glucose ratio - 2:1
Accumulation ratio - 30000:1

45
Q

What uses SGLT1 ?

A

Intestinal uptake of glucose

46
Q

SGLT2

A

Km - 1.6
Affinity - Low
Na+/glucose ratio - 1:1
Accumulation ratio - 200:1

47
Q

What uses GLUT2 Facilitated diffusion ?

A

Trans-epithelial glucose transport

48
Q

Diuretics use

A

They increase urine output by the kidneys
Promote diuresis

Treatment for : high blood pressure and excessive fluid retention

49
Q

Side effects of diuretics

A

Loop diuretics such as Furosemide
Increased urinary excretion of potassium

50
Q

Cardiac glycoside toxicity and blood potassium concentration

A

Patients on digoxin(narrow therapeutic index)who start diuretics (furosemide) – may become hypokalaemic.

A reduction in competition between K+ and digoxin results in increased digoxin binding to the sodium pump.
(though plasma concentration is unchanged)

Because of the very narrow therapeutic index, the patient develops digoxin toxicity.

51
Q

Emergency treatment for digoxin toxicity

A

Administer a digoxin binding antibody

Digibind rapidly binds to the digoxin causing it to dissociate from the sodium pump reversing the toxicity associated with the increased sodium pump inhibition caused by the hypokalaemia.