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Y1 - ICPP > Lecture 4 - Pores, Channels And Transporters > Flashcards

Lecture 4 - Pores, Channels And Transporters Flashcards

1
Q

What is active transport?

A

Transport of ions or molecules against the concentration gradient using energy directly or indirectly from hydrolysis of ATP

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2
Q

What is primary active transport?

A

Active transport which directly uses the energy from the hydrolysis of ATP to transport molecules against their concentration gradient

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3
Q

What is secondary active transport?

A

Type of Co-transporter

When an electrochemical gradient is set up by an ATPase is then used to transport another ion or solute against its gradient

Use a pre-existing electrochemical gradient to co-transport a molecule against its concentration gradient

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4
Q

What are the 4 primary active transporters i need to know?

A

Na+/K+ pump (sodium pump)
Calcium ATPases (PMCA and SERCA)
K+/H+ ATPase (Proton pump)
F1/F0 ATPase (ATP synthase, doesn’t hydrolyse ATP)

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5
Q

Where is the SERCA transporter protein located?

A

Sarcoplasmic reticulum of skeletal muscle cells

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6
Q

What type of co-transport is occurring with a Na+/K+ ATPase or sodium pump?

A

Antiport

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7
Q

Where a sodium pump is concerned, what are the relative concentrations of Na+ and K+ inside and outside of the cell?

A

K+ high inside cell low outside

Na+ high outside cell, low inside

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8
Q

With the Na+/K+ ATPase (sodium pump), how many sodium ions and how many potassium ions are being transported?

A

3 Na+
2 K+

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9
Q

Which direction is Na+ being actively transported and which direction is K+ being actively transported with the sodium pump?

A

2 K+ pumped into cell
3 Na+ pumped out of cell

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10
Q

Why is a sodium pump an example of a primary active transporter?

A

Uses energy directly from the hydrolysis of ATP to actively transport both K+ and Na+ against their gradients

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11
Q

Which amino acid on the sodium pump gets phosphorylated from the Pi from hydrolysed ATP?

A

Phosphorylates Aspartate
Makes phosphoenzyme intermediate

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12
Q

How does the sodium pump work?

A

ATP hydrolysed (Aspartate phosphorylated) causes conformational change
3 Na+ taken into their high affinity sites
Conformational change opens the protein so Na+ can be released out of the cell
Conformational change allows 2 K+ to bind to pump
Conformational change opens pump to inside the cell phosphate released causing K+ site to have low affinity for K+ so released into cell

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13
Q

What is the structure of the sodium pump?

A

2 subunits
Alpha and beta

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14
Q

What is the function of the alpha subunit of the sodium pump?

A

Where all the work is done:
Where phosphate binds and where ions pumped

Has Ouabain receptor

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15
Q

What is the function of the Beta subunit of the sodium pump?

A

A glycoprotein which puts sodium pump on plasma membrane of cell

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16
Q

What is Ouabain?

A

Cardiac glycoside

Binds to sodium pump preventing it from functioning

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17
Q

What is the function of the Na+/K+ ATPase (Na+ pump)

A

Forms Na+ and K+ gradients for electrical excitability

Drives secondary active transport (set up electrochemical gradient)

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18
Q

What is the main contributor to maintaining membrane resting potential?

A

Leaky K+ channels

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19
Q

Which ion is toxic to the heart?

A

K+

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20
Q

What is the normally K+ serum levels in the blood?

A

4mM

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21
Q

The concentrations of which ions are normally always greater outside the cell compared to inside?

A

Ca2+
Na+
Cl-

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22
Q

Why is calcium toxic to cells?

A

Activates enzymes that shouldn’t be activated

Calcium phosphate crystallises in the cell killing the cell

Calcium influx in mitochondria causes apoptosis

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23
Q

Why is it useful the concentration of calcium being so much lower inside the cell compared to the outside?

A

Can utilise calcium for certain process

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24
Q

What is another name for a plasma membrane Ca2+ ATPase?

A

PMCA

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25
Q

What is the role of PMCA?
(Plasm membrane Ca2+ ATPase)?

A

Exclude Ca2+ ions from the cell

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26
Q

What type of transport does the PMCA primary active transporter use?

A

Uniport

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27
Q

What other transporter protein expels calcium from the cell?

A

NCX (Na+/Ca2+)

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28
Q

What is the difference between PMCA and NCX?

A

NCX = Secondary active transporter + antiporter

PMCA = Primary active transporter + Uniporter

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29
Q

How does the affinity and capacity of PMCA compare to NCX?

A

PMCA = High affinity BUT Low Capacity (Ca2+ binds well but cant move a lot)

NCX = Low affinity BUT High capacity (Ca2+ doesn’t bind well but can move lots at once)

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30
Q

What is the name of the calcium transporter found on the membrane of the sarcoplasmic reticulum?

A

SERCA
(SarcoEndoplasmic reticulum Ca2+ ATPase)

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31
Q

What type of Ca2+ transporter exists in the mitochondria?

A

Ca2+ uniporter

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32
Q

What is the pathology of Duchenne muscular dystrophy?

A

Too much Ca2+ enters into mitochondria
Water drawn into mitochondria
Mitochondria burst
Replaced with adipocytes

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33
Q

How can Ca2+ entering mitochondria cause cell death?

A

Ca2+ can activate caspases causing apoptosis

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34
Q

What is unique about the F1/F0 ATPase (ATP synthase)?

A

Synthesises ATP rather than hydrolysing it

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35
Q

Briefly describe how the F1/F0 ATPase (ATP synthase) transporter works:

A

Proton gradient from inter membrane space to matrix exists
H+ binds to F0 which rotates allowing H+ to pass back into the matrix
F1 rotates rotates and Phosphorylates ADP and Pi to ATP

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36
Q

How many H+ must pass through the F1/F0 ATPase complex to produce 1 ATP molecule?

A

3 H+ = 1 ATP

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37
Q

What type of transporter is Sodium Glucose Cotransporter 1/2 (SGLT-1 or SGLT-2)?

A

Secondary active transporter
Symporter

38
Q

How many Na+ does SGLT-1 move in for every glucose?

A

2 Na+

39
Q

How many Na+ does SGLT-2 move in for every glucose?

A

1 Na+

40
Q

What is the importance of Organic Anion Transporter (OAT) and Organic Cation Transporter (OCT)?

A

How many drugs enter into cells

41
Q

What is the role of the Na+/Ca2+ exchanger (NCX)?

A

Expels intracellular Ca2+ from cell during recovery (while cell is repolarising)

42
Q

What type of transporter is NCX?

A

Antiporter
Secondary active transporter

43
Q

How many molecules of Na+ are moved into the cell and how many Ca2+ ions are moved out of the cell per cycle by NCX?

A

3 Na+ in
1 Ca2+ out

44
Q

How does charge within the cell usually change as NCX is active?

A

Becomes more positive by +1 each exchange (3+ in cell , 2+ out of cell net gain of +1)

45
Q

What is reperfusion?

A

Restoration of blood flow to a region normally following an arterial occlusion allowing for wastes to begin to be removed from the tissues

46
Q

What happens to NCX when the membrane is polarised?

A

Ca2+ pumped into cell
Na+ pumped out

Function of NCX flips

47
Q

How does NCX function in ischaemia?

A

Blood supply cut of leads to lack of O2 so depletion of ATP
Sodium pump cant act
Na+ accumulates in cell and cell becomes very positive so is depolarises
Depolarised membrane causes NCX function to flip so 3 Na+ expelled from cell as 1 Ca2+ pumped into cell
Ca2+ builds up in cell, cell dies

48
Q

What are the 2 primary active transport methods of controlling resting Ca2+ conc in the cell?

A

PMCA
SERCA

49
Q

What is the secondary active transport method of controlling resting calcium concentration?

A

NCX

50
Q

What is the method of controlling resting calcium concentration via facilitated diffusion?

A

Mitochondrial Ca2+ uniports
Buffer potentially damaging calcium concentrations

51
Q

What does the Na+/H+ exchanger transport? (NHE)

A

1 Na+ into cell
1 H+ out of cell

No net change in charge

52
Q

What type of transport is used by NHE (Sodium proton exchanger)?

A

Secondary active transport
Antiport

53
Q

What is the role of NHE (Na/H+ exchanger)?

A

Regulates pH
Regulates cell volume

54
Q

How does NHE regulate cell volume?

A

As sodium brought into cell, water is brought with it

55
Q

What is Amiloride?

A

Drug that targets the NHE

56
Q

What is the function of amiloride?

A

Inhibits NHE
Prevents Na+ and water being drawn back into kidney cells

Is a diuretic (does take potassium with it)

57
Q

What is the importance of the sodium pump (Na+/K+ ATPase) carrier protein in regulating cellular pH?

A

Establishes Na+ gradient (electrochemical gradient) so secondary active transport can take place at other transporters to regulate pH

58
Q

Which transporters lead to acid extrusion from a cell?

A

NHE
Sodium Bicarbonate Chloride transporter

59
Q

Which transporters cause alkali influx into cells?

A

Sodium Bicarbonate Chloride transporter (NBC)
Sodium Bicarbonate transporter

60
Q

Which transporter extrudes alkali from then cell no which cells are they commonly in?

A

Anion exchanger (AE)
Like band 3 in RBCs

61
Q

Where in the kidney is blood glucose controlled?

A

Nephron

62
Q

What would happen if selective reabsorption did not happen in the nephron?

A

Na+, HCO3-, H2O and glucose would all be lost from the body in urine
RAPID DEHYDRATION AND COMA

63
Q

What type of kinetics do carrier proteins experience and why?

A

Michaelis Menton Kinetics
All sites get saturated and rate conformational changes occurring can’t change

64
Q

In the gut (enterocyte) which glucose transporter is present on the apical surface?

A

SGLT-1
(Sodium glucose co-transporter 1)

65
Q

In the gut (enterocyte) which glucose transporter is found on the base lateral surface?

A

GLUT-2

66
Q

Where SGLT-1 is present, what other transporter will always be found on the basolateral surface?

A

GLUT-2

67
Q

What type of active transport does the K+/H+ ATPase transporter do?
(Proton pump)

A

Primary active transport
Directly uses energy from hydrolysis of ATP

68
Q

What is the role of the K+/H+ ATPase in the enterocyte?

A

Sets up proton gradient
So proton and sucrose can by symporter from gut lumen into enterocyte across Sucrose-proton cotransporter

69
Q

What type of active transport is used by the sucrose-H+ Cotransport at the gut?

A

Secondary active transport

70
Q

How many sections are there of the PCT of the nephron?

A

3

71
Q

Which SGLT transporter is used in segment 1 of the PCT to transport glucose back in to the epithelial cell?

A

SGLT2

72
Q

What SGLT transporter is used in segment 2 and 3 in the PCT to reabsorb glucose into the epithelial cells?

A

SGLT1

73
Q

Which glucose exporter is used to put glucose back in the blood in segment 1 in the PCT?

A

GLUT 2

74
Q

Which glucose exporter is used to put glucose back in the blood in segment 2 and 3 of the PCT?

A

GLUT1

75
Q

Action of SGLT2 and SGLT1 inhibitors in Type 2 diabetes Mellitus?

A

SGLT2 inhibitors inhibit glucoses uptake in kidney

SGLT1 inhibitors inhibit intestinal absorption

76
Q

What is phlorizin?

A

SGLT2 inhibitor

77
Q

What is the main glucose transporter in the liver?

A

GLUT 2

78
Q

What is the main glucose transporter in muscles and adipose?

A

GLUT 4

79
Q

What hormone regulates expression of GLUT 4?

A

Insulin promotes

80
Q

Where is GLUT1 found?

A

CNS (Astrocytes)

81
Q

What are MCT proteins?

A

Symporters of H+ and lactate ions from Astrocyte to neurone

82
Q

What pathways is glucose transported in the CNS?

A

Glucose into Astrocyte via GLUT1
GLucose converted to lactate
Lactate transported to neurone via MCT

Glucose via GLUT1 via endothelial cells into interstitial space
GLUT3 into neurone

83
Q

What type of transport happens across GLUT transporters?

A

Facilitated diffusion

84
Q

What drives the transport of glucose across SGLT transporters?

A

Na+/K+ ATPases

85
Q

How does glucose uptake into skeletal muscles and adipose tissue increase with insulin?

A

Insulin binds to Tyrosine kinase receptor
Receptor phosphylates itself
Activates secondary messenger cascade
Vesicles containing GLUT 4 proteins fuse to plasma membrane of cells

86
Q

Which glucose transporter is present at the blood brain barrier?

A

GLUT-1

87
Q

Which glucose transporter is present in neurones?

A

GLUT-3

88
Q

Why it essential that GLUT-1 and GLUT-3 have very low Km for glucose?

A

So brain and neurones receive as much glucose as possible to prevent death

89
Q

Describe how glucose is transported from the gut lumen into the blood:

A

Na+/K+ ATPase pumps 3 Na+ out of cell into blood and 2K+ from blood into cell (basolateral surface)
SGLT1 Moves 2 Na+ with 1 glucose from apical surface into cell
GLUT2 moves glucose into the blood from the cell

90
Q

Which has a lower Km, SGLT1 or SGLT2?

A

SGLT 1 since it works at lower concentrations (think of the kidney PCT)

91
Q

Which glucose transporter reabsorb most of the glucose back into the PCT?

A

SGLT2

Y1 - ICPP (23 decks)

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