L8: Membrane Transport Flashcards

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1
Q

What are the two types of transport across biological membranes?

A
  • Active (needs ATP)
  • Passive (doesn’t require ATP)
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2
Q

When is ATP required in transport?

A
  • Against a concentration or electrochemical gradient, ATP is required
  • Down a concentration or electrochemical gradient, ATP is not required
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3
Q

What are the two types of passive transport?

A
  • Simple diffusion - no membrane proteins involved and driven by concentration gradients
  • Facilitated diffusion - membrane proteins involved and driven by concentration gradients
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4
Q

Describe simple diffusion

A
  • Molecules move stochastically (across the membrane in both directions)
  • Molecules move down a concentration gradient (from high to low concentration) until equilibrium is reached and there is no gradient
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5
Q

What factors determine solute movement across a membrane in simple diffusion?

A
  • Concentration gradient
  • Size of the molecule
  • Hydrophobicity/charge
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6
Q

Can hydrophobic molecules diffuse across the plasma membrane?

A
  • The plasma membrane is permeable to hydrophobic molecules
  • Able to pass directly through the hydrophobic core of the lipid bilayer - complementary
  • e.g. O2, CO2, N2 and steroid hormones
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7
Q

Can small uncharged polar molecules diffuse through the plasma membrane?

A
  • Can ever so slightly pass through the membrane, but generally not due to their polar nature - cannot pass through the non-polar, hydrophobic centre of the lipid bilayer
  • e.g. H20, urea and glycerol
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8
Q

Can large uncharged polar molecules diffuse through the plasma membrane?

A
  • Cannot diffuse through the membrane
  • The plasma membrane is highly impermeable to these molecules
  • e.g. glucose and sucrose
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9
Q

Can ions diffuse through the plasma membrane?

A
  • Highly impermeable to ions - cannot pass through the non-polar hydrophobic centre of the lipid bilayer as the ions are hydrophilic and repelled by the hydrocarbon fatty acid tails
  • e.g. H+, Na+, K+, Ca2+ and Cl-
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10
Q

What are inorganic ions and small molecules required for in cells?

A
  • Regulation of intracellular ion concentrations
  • Uptake of nutrients
  • Excretion of metabolic waste products
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11
Q

What is facilitated diffusion?

A

Diffusion down a concentration gradient involving membrane proteins for inorganic ion/smaller molecules

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12
Q

What are the two types of membrane protein?

A
  • Channel proteins - discriminate on what they allow through based on size and charge of the ion
  • Uniporter carrier proteins - involve a binding site for solutes
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13
Q

Describe what an electrochemical gradient is and how they function

A
  • An electrochemical gradient combines the concentration gradient and membrane potential
  • With a negatively charged membrane potential, this enhances the electrochemical gradient, meaning positively charged ions are more likely to move across the membrane
  • With a positively charged membrane potential, this reduces the electrochemical gradient, reducing the movement of the positively charged solute across the membrane
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14
Q

What features do ion channels exhibit?

A
  • Exhibit selectivity
  • Driven by a concentration/electrochemical gradient
  • Fast - transport up to 10^7 molecules per second
  • May be regulated (open and close in response to a stimulus)
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15
Q

Name some different ion channels?

A
  • Voltage gated
  • Ligand-gated (extracellular ligand)
  • Ligand- gated (intracellular ligand)
  • Mechanically gated
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16
Q

What is the most common ion channel?

A

K+ ion channel

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17
Q

Describe the K+ ion channel

A
  • Continuously open - not gated
  • Highly selective for K+
  • Moves K+ very quickly from inside the cell where K+ is hydrated
  • K+ is dehydrated in the ‘vestibule’ of the channel protein and the carboxyl oxygens of amino acids line up and selectively filter the K+ out of the cell, rehydrating K+
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18
Q

What is an example of a uniporter carrier protein?

A

Glucose transporter (Glut2) in gut epithelia

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19
Q

How does the glucose uniporter carrier protein work?

A
  • Highly selective to glucose
  • Has a binding site that will recognise and bind glucose
  • The binding of glucose causes a conformational change in the protein, causing the glucose to move to the other side
  • Movement down a concentration gradient
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20
Q

How do uniporter carrier proteins differ to channel proteins?

A
  • Uniporter carrier proteins are much slower than channel proteins - <1000 molecules per second
  • Because of the requirement for a conformational change in the protein
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21
Q

Describe the selectivity in a glucose transporter (Gluts)

A
  • Uniporters (only transport glucose)
  • Expressed by most cell types
  • 12 pass membrane spanning proteins
  • Alternate between two conformations
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22
Q

What happens if there is a Glut1 deficiency?

A

Syndrome characterised by seizures, microcephaly and retarded development

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23
Q

Describe the transport of glucose into a erythrocyte

A
  • Glucose concentration is higher in the blood than the erythrocyte
  • Glucose is transported down a concentration gradient into the erythrocyte by the Glut1 uniporter
  • Glut1 can work in both directions- leads to equilibrium - so the concentration gradient has to be maintained
  • Glucose is converted into glucose-6-phosphate by the addition of phosphate
  • Glucose-6-phosphate is not recognised by Glut1 making it a one-directional transport - not able to bind
24
Q

Why do cells maintain electrochemical gradients?

A
  • Drive transport of molecules across membrane
  • Maintain osmotic balance (water balance)
  • Electrical forces inside and outside the cell must be balanced (though small localised differences at the plasma membrane are allowed)
25
Q

Why is active transport so important?

A

Without active transport (req. ATP) to maintain electrochemical gradients, ions would flow down their gradients through channels, disturbing osmotic balance

26
Q

What is the essential feature of active transport?

A
  • Moves solutes against their electrochemical gradients
  • To achieve this energy is required
27
Q

What type of active transport is an ATP driven-pump?

A

Primary active transport

28
Q

How is the energy for active transport provided?

A
  • ATP-driven pumps - couple the transport of a solute against its gradient to the hydrolysis of ATP
  • Coupled transporters - couple the transport of one solute with the gradient to another against the gradient
  • Light-driven pumps - couple the transport of a solute against its gradients to the input of energy from light
29
Q

What type of active transport is a coupled transporter?

A

Secondary active transport

30
Q

What is the difference between primary and secondary active transport?

A
  • Primary involves ATP directly
  • Secondary does not involve ATP directly and uses another gradient
31
Q

What is an example of an ATP-driven pump?

A

The Na+ and K+ electrochemical gradient/pump

32
Q

Are there more Na+ ions intracellularly or extracellularly?

A

Extracellularly

33
Q

Are there more K+ ions intracellularly or extracellularly?

A

Intracellularly

34
Q

Why is the Na+/K+ pump so important?

A
  • Absence of sodium ions pumped out and potassium ions in causes the ions to flow down their gradients
  • This affects the osmotic balance and prevents ‘secondary’ active transport
35
Q

What maintain the concentration difference between Na+ and K+?

A

Sodium-potassium ATPase

36
Q

What % of a cell’s total energy consumption if used in the ATPase pump?

A

30%

37
Q

How is the sodium-potassium ATPase pump electrochemical gradient maintained?

A
  • Operates continuously to expel Na+ that enters cell through other carrier proteins and channels
  • Hydrolyses ATP to ADP and Pi - both an enzyme and carrier protein
  • Couples the export of Na+ to the import of K+
38
Q

Where is the ATPase pump found?

A

Every plasma membrane of all eukaryotic cells

39
Q

Describe how the Na+/K+ ATPase mechanism works?
(For Na+)

A
  • Both an alpha and a beta
  • The beta chain trafficks the pump to the plasma membrane
  • 3x Na+ ions bind to the open pump on the inside
  • Pump hydrolyses the ATP into ADP and the terminal phosphate (-vely charged) binds to the pump - phosphorylates the pump
  • Na+ dependent phosphorylation causes pump to undergo conformational change
  • Sodium ions transported across the membrane and released into the extracellular environment
40
Q

Describe how the Na+/K+ ATPase mechanism works?
(For K+)

A
  • 2x K+ ions are able to bind to the pump as Na+ is released
    This dephosphorylates the pump
  • K+ dependent phosphorylation causes the pump to return to its original conformation
  • K+ is transferred across the membrane and released into the intracellular environment
41
Q

How does secondary active transport work?

A
  • Moves solutes against the concentration/electrochemical gradient by coupling transport to Na+ gradient created by the Na+/K+ ATPase
  • Does not depend on the hydrolysis of ATP
42
Q

What is a symporter, in coupled transporters? Give an example

A
  • Molecules move in the same direction
  • Sodium down its electrochemical gradient with glucose at the same time
43
Q

What is an antiporter, in coupled transporters? Give an example

A
  • Molecules move in different/opposite directions
  • Sodium down its electrochemical gradient and calcium against its electrochemical gradient
44
Q

Describe how the Na+/glucose symporter works

A
  • High Na+ in the gut and low in the cell
  • High glucose in the cell and low in the gut
  • Glucose has to move against its concentration gradient into the gut
  • Binding on glucose and Na+ is co-operative (binding on glucose is dependent on Na+)
  • Na+ concentration is much higher outside of the cell, so glucose binds to the same carrier protein as Na+ and is more likely to bind this way
  • Conformational change of the carrier protein
  • Releases both Na+ and glucose into the gut epithelial cell
  • Net flow into the cell
  • Uses energy provided by the sodium electrochemical gradient
45
Q

Where is the Na+/glucose symporter located?

A
  • Luminal side of the epithelial cell on the GI tract
  • Glucose concentration is higher in the epithelial cells than in the lumen
46
Q

Why are glucose symporters required for the absorption of glucose from the GI tract?

A

Epithelial cells are very tightly joined together by tight junctions between them, which restricts paracellular movement
- Transcellular movement required for small molecules to transfer between the blood and gut

47
Q

Describe the overall process for the absorption of glucose

A
  • Na+ gradient is created by the Na+/K+ ATPase (primary active transport) - provides the energy needed to move glucose from low to high concentration in the cell
  • Na+/glucose symporter transports glucose into the epithelial cells (against its concentration gradient) by utilising the Na+ electrochemical gradient (secondary
    active transport)
  • Glut2 (uniporter) transports glucose out of the cells (along its concentration gradient) and into the blood supply (facilitated diffusion) - because other processes mean glucose concentration is higher in the epithelial cells than in the blood
48
Q

Where is the Na+/glucose symporter located?

A

Apical membrane on the lumen of the GI tract

49
Q

Where is Glut2 located?

A

Basolateral membrane

50
Q

Describe the Na+/Ca2+ antiporter

A
  • Uses the sodium gradient
  • 3x Na+ moved out of the cell using its electrochemical gradient
  • 1x Ca2+ moved into the cell against its gradient
51
Q

What is the Na+/Ca2+ antiporter important for?

A
  • Cardiac muscle
  • Cardiac muscle cell contraction is triggered by a rise in intracellular calcium
  • The antiporter reduces intracellular Ca2+ concentration, which reduces the strength of cardiac muscle contraction - modulate contraction
52
Q

What drug has an inhibitory effect on the Na+/K+ ATPase?

A

Ouabain

53
Q

What effect would ouabain have on cardiac contractility?

A
  • The concentration of Na+ pumped out of the cell is reduced as the ATPase is inhibited
  • Means an increase in intracellular Na+
  • There is a reduction in the Na+ gradient so the effectiveness of the the Na+/Ca2+ antiporter is reduced, so less Ca2+ is transported out of the cell
  • Maintains intracellular Ca2+ concentration, increasing cardiac muscle cell contractility
54
Q

When is ouabain used in a clinical setting?

A

Improve cardiac contractility to prevent heart failure

55
Q

The SGLT2 transporter facilitates which types of transport?

A
  • Secondary active transport
  • The glucose is moving against the concentration gradient , but does not use ATP directly
  • ATP provided by the sodium electrochemical gradient maintained by the sodium potassium pump
56
Q

What is the function of SGLT2 transporters?

A
  • Takes glucose out of the urine and transports it back into the blood
  • Regulates blood glucose concentration
  • Useful for treating diabetes - limits blood glucose concentration by allowing more to be excreted in the urine
57
Q

Draw a diagram to summarise membrane transport

A