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Biochemistry III > Membrane transporters > Flashcards

Membrane transporters Flashcards

1
Q

What are the most permeable ions?

A

Hydrophpbic molecules

Such as: O2, H2, H2O

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2
Q

What are the different types of transport ATPases?

A

P-Type

V-Type

F-Type

ABC transporters

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3
Q

What kind of proteins are P-type ATPases?

A

integral membrane

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4
Q

What are the different domains of the P-Type ATPases?

A

T domain: transport

N domain: ATP/ADP binding

P domain: phosphorylation

A domain : phosphatase activity (regulates N and P)

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5
Q

What is the generic description of the P-Type ATPases?

A

during their function they are phosphorylated/dephosphorylated via the hydrolysis of ATP

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6
Q

What are some examples of P-Type ATPases?

A

Na, K-ATPase

K, H-ATPase

SERCA ATPase

PMCA (plasma membrane calcium ATPase)

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7
Q

What are the different isoforms of the sodium potassium pump?

A

α1

α2

α3

α4

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8
Q

What is the K, H-ATPase respondible for?

A

K+ absorption

H+ excretion

(in stomach parietal cells)

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9
Q

Where can SERCA 1 be found?

A

striated muscle

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10
Q

Where can SERCA 2 be found?

A

smooth muscle, striated muscle, heart muscle

(phospholambane)

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11
Q

Where can SERCA 3 be found?

A

platelets, endothelial cells and other non muscle cells

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12
Q

What are the general PMCA’s?

A

PMCA 1 & 4

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13
Q

What is PMCA 2 specific for ?

A

neuronal-

has a higher affinity for cAMP phosphorylation than PMCA 4

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14
Q

Where is PMCA 4 present?

A

striated muscle, brain

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15
Q

What are the steps of the mechanism of which the Na, K Pump works?

A
  1. transporters bind 3 Na+ from the inside of the cell
  2. phosphorylation favors P-enzII
  3. transporters release the 3 Na+ outside of the cell, and bind 2 K+ from outside of the cell
  4. Dephosphorylation EnzI
  5. Transporters release the 2 K+ inside of the cell
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16
Q

What are the relations regarding affinity for Na+ and ATP in regards to EI and E2? (sodium potassium pump function)

A

EI HIGH affinity for Na+ and ATP

EII LOW affinity for Na+ and ATP

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17
Q

Draw cycle displaying the mechanism of the sodium potassium pump in action

A
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18
Q

Most of the function is done by which subunit?

A

α “does all the work”

the beta subunit is present to give stability to the α subunit

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19
Q

How many subunits does the sodium potassium pump have?

A

at least 2 but maybe 3:

α → 4 isoforms

beta → 3 isoforms

FXYD

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20
Q

What is the function of the FXYD subunit?

A
  • regulates the transport kinetics of the α subunit
  • not present in all tissues
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21
Q

Ouabain effects

A

Na K ATPase inhibition

this causes an increased intracellular [Na] which is beneficial in the heart because it will reverse the Na+ Ca2+ exchanger and cause an increase of Ca2+ within the cell

causes more forceful contraction

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22
Q

Where is the α1 subunit located?

A

all tissues (heart also), kidney outer medulla ONLY α1

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23
Q

Where is the α2 subunit located?

A

striated muscle

smooth muscle

heart (t tubules)

brain (astrocytes)

adipocytes

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24
Q

Where is the α3 subunit located?

A

brain (neurons)

heart (small amount)

ovary

leukocytes

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25
Q

Where is the α4 subunit located?

A

testis

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26
Q

Where are endogenous cardiac glycosides synthesized and what is their function?

A

they are a steroid structure synthesized in the zona fasciculata from progesterone

Function: regulate vascular tone

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27
Q

When can endogenous cardiac glycosides (such as Ouabain) be used? What is the mechanism? What can happen with sustained treatment?

A

in certain forms of hypertension

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28
Q

FXYD subunit is a tissue specifc regulator in what organs?

A

heart

kidney

pancreas

foetal liver

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29
Q

What is the FXYD subunit in the heart and what is its effect?

A

FXYD1

when dephosphorylated it decreases the Na+ affinity of the α-subunit

β1 receptor stimulation

PKA stimulation →phosphorylation of phospholemman → [Na+]i [Ca2+]i ↓

prevention of arrythmia

30
Q

What is the FXYD subunit in the kidney and what is its function?

A

FXYD2

↑ affinity of the enzyme for ATP

BUT only moderately in order to increase the pump activity, too large of an affinity would actually a decrease in ATP

31
Q

What is the short term regulation of the sodium potassium pump?

A

direct effects on the enzyme or changes in the translocation of the enzyme between the plasma membrane and the intracellular membranes

32
Q

What is the long term regulation of the sodium potassium pump?

A

de novo synthesis of the Na, ATPase is influenced

steroid hormones

catecholamines

insulin

33
Q

What are two corticosteroids that play a role in the regulation and what are their effects?

A

mineralocorticoide aldosterone

glucocorticoide dexamethazone

Long term effect:

↑ expression of the Na+ pump

↑ expression of the α and β subunit mRNA type-I rececptor andglucocorticoide type-II receptor (nuclear)

34
Q

Where are the effects of

mineralocorticoide aldosterone

glucocorticoide dexamethazone ?

A

several tissues (kidney, brain, heart, skeletal m, vascular smooth m)

35
Q

What is Aldosterones most important role?

A

adpation in the kidney to a decreased Na+ or increased K+ intake

36
Q

What is the long term upregulation of aldosterone?

A

isoform-specific

α1- vascular smooth muscle

α2- heart

α3- brain

37
Q

What is the short term effect of aldosterone?

A

↑ activity of the enzyme

translocation of the pump to the plasma membrane

and/or

↑ in the affinity of the enzyme to Na+

38
Q

What are some examples of Catecholamines?

A

epinephrine

norepinephrine

dopamine

often antagonistic

39
Q

Where is dopamine synthesized?

A

kidney proximal tubules

(both paracrin and autocrin)

dopamine is a natriuretic factor

40
Q

What is the effect of dopamine?

A

Na,K ATPase INHIBITION

Location: proximal tubule + cortical collecting tubules

plus other organs (arteries, retina, small intestine, neurons)

41
Q

What is the effect of dopamine in the kidney? What are the receptors?

A

decreased Na+ reabsorption

physiological importance under high salt intake

Receptors: D1 and D2 which are phosphorylated by PKA and PKC

42
Q

What is the effect of NE, and E? And what is their mechanism of action?

A

stimulation of the pump

Mechanism:

  • direct stimulation of the enzyme or chelating inhibitory ions
  • α and β receptors → stimulated by PKA and PKC
43
Q

What are the tissue specific effects of epinephrine in skeletal muscle?

A

stimulation of K+ uptake

↓ hyperkalaemia after muscle exercise

44
Q

What are the tissue specific effects of norepinephrine in the kidney?

A

dopamine ANTAGONIST

Na+ reabsorption

45
Q

What are the tissue specific effects of norepinephrine in the brain?

A

reestablishment of the ion gradients after nerve impulse

46
Q

What is the short term effect of insulin?

A

stimulation of the Na,K ATPase

in skeletal muscle only in oxidative, slow twitch muscles → translocation of the enzyme to the plasma membrane

47
Q

What is the long term regulation of insulin?

A

↑ or ↓ expression

48
Q

What are some examples of secondary active transport molecules that accompany sodium in the Na+ cotransports?

A

Glucose uptake

Amino acid uptake

choline uptake into cholinergic nerve terminals

E, NE, Dopamine, Serotonin uptake by axon terminals

H+ exchanger

Ca2+ exchanger

which can all be inhibited by Ouabain

49
Q

What is important to note about the Na+ H+ exchanger? (NHE)

A

it is NOT electrogenic

50
Q

How many isoforms does the Na+ H+ exchanger have?

A

5 - 12 transmembrane region

51
Q

Where is NHE 1 located?

A

general (basolateral membrane)

52
Q

Where is NHE 3 located?

A

epithelial cells; apical membrane

53
Q

Where is NHE 5 located?

A

brain

testis

54
Q

Draw a schematic representation of the mechanism of which neurotransmitter are uptook by synaptic vesicles

A
55
Q

What cation do vesicular neurotransmitter antiporters use?

A

H+

they are proton antiports

also called vesicular membrane antiporters (VMAT)

56
Q

Where is VMAT1 located?

A

brain

neuroendicrine cells

cholinergic synapses

57
Q

Where is VMAT2 located?

A

neurons

adrenal chromaffin cells

58
Q

Where is VAChT located?

A

cholinergic synapses

59
Q

What are vesicular neurotransmitter antiporters inhibited by?

A

H+ ionophores

60
Q

How many transmembrane segments do vesicular neurotransmitter antiporters have?

A

12

broad selectivity: E, NE, DOP, SER

61
Q

What do ABC transporters bind?

A
  1. AA
  2. Peptides
  3. Ions
  4. Lipids
  5. Bile acids
  6. drugs
62
Q

What is the mechanism of the ABC transporter? What are they dependent on?

A

transports against the concentration gradient

ATP

63
Q

Where are ABC transporters present?

A

plasma membrae

endoplasmic reticulum

mitochondrial membrane

64
Q

What is an example of a important ABC transporter? What can happen if a mutation occurrs?

A

CFTR transporter - Cl- channel

if a mutation occurrs cystic fibrosis may be the outcome

65
Q

What are the families of the ABC transporter?

A

ABCA

ABCB

ABCC

and further subfamilies

66
Q

What is the function of the ABCA1 family?

A

cholesterol, phospholipid transport

reverse cholesterol transport

67
Q

What is the function of the ABCA3 transporter?

A

translocation of pulmonary surfactant lipids

mutation: respiratory distress szindroma

68
Q

What is the function of the ABCB1 (MDR1, multidrug resistance transporter)

A

transport of lipophylic compounds→ protection against toxins

increased expression in tumor cells: drug resistance

69
Q

What is the function of ABCB4 transporter? Where are they located?

A

Function: bile acid, phospholipid transport into bile

Location: canalicular membrane of hepatocytes

70
Q

ABCC1 transporter

A

phospholipids

glutathione conjugates

anti-tumor drugs

71
Q

CFTR

A

Cl- flux in the apical membrane of epithelial cells

mutation: cystic fibrosis (thick mucus in the bronchi and pancreas → blockage, infection , foetal ileus

Biochemistry III (8 decks)

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