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Biochemistry III > Membrane transporters > Flashcards

Membrane transporters Flashcards

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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
Where is the **α4 subunit** located?
testis
26
Where are **endogenous cardiac glycosides** synthesized and what is their function?
they are a *steroid structure* synthesized in the z*ona fasciculata* from *progesterone* ## Footnote Function: regulate vascular tone
27
When can endogenous cardiac glycosides (such as Ouabain) be used? What is the mechanism? What can happen with sustained treatment?
in certain forms of hypertension
28
FXYD subunit is a tissue specifc regulator in what organs?
heart kidney pancreas foetal liver
29
What is the FXYD subunit in the heart and what is its effect?
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
What is the FXYD subunit in the kidney and what is its function?
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
What is the short term regulation of the sodium potassium pump?
direct effects on the enzyme or changes in the translocation of the enzyme between the plasma membrane and the intracellular membranes
32
What is the long term regulation of the sodium potassium pump?
de novo synthesis of the Na, ATPase is influenced **steroid hormones** **catecholamines** **insulin**
33
What are two corticosteroids that play a role in the regulation and what are their effects?
**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
Where are the effects of mineralocorticoide aldosterone glucocorticoide dexamethazone ?
several tissues (kidney, brain, heart, skeletal m, vascular smooth m)
35
What is **Aldosterones** most important role?
adpation in the kidney to a **decreased Na+** or **increased K+ intake**
36
What is the long term **upregulation** of **aldosterone**?
isoform-specific ## Footnote α1- vascular smooth muscle α2- heart α3- brain
37
What is the **short term** effect of **aldosterone**?
↑ activity of the enzyme translocation of the pump to the plasma membrane and/or ↑ in the affinity of the enzyme to Na+
38
What are some examples of Catecholamines?
epinephrine norepinephrine dopamine *often antagonistic*
39
Where is **dopamine** synthesized?
**kidney proximal tubules** (both paracrin and autocrin) dopamine is a natriuretic factor
40
What is the **effect** of **dopamine**?
Na,K ATPase **INHIBITION** ## Footnote Location: proximal tubule + cortical collecting tubules plus other organs (arteries, retina, small intestine, neurons)
41
What is the effect of **dopamine** in the kidney? What are the receptors?
decreased Na+ reabsorption *physiological importance under high salt intake* Receptors: D1 and D2 which are phosphorylated by PKA and PKC
42
What is the effect of **NE,** and **E**? And what is their mechanism of action?
**stimulation** of the pump Mechanism: * direct stimulation of the enzyme or chelating inhibitory ions * α and β receptors → stimulated by PKA and PKC
43
What are the **tissue specific effects** of **epinephrine** in skeletal muscle?
**stimulation** of K+ uptake ↓ hyperkalaemia after muscle exercise
44
What are the **tissue specific effects** of **norepinephrine** in the kidney?
dopamine ANTAGONIST Na+ **reabsorption**
45
What are the **tissue specific effects** of norepinephrine in the **brain**?
reestablishment of the ion gradients after nerve impulse
46
What is the **short term effect** of **insulin**?
**stimulation** of the Na,K ATPase in skeletal muscle only in oxidative, slow twitch muscles → translocation of the enzyme to the plasma membrane
47
What is the **long term** regulation of **insulin**?
↑ or ↓ expression
48
What are some examples of secondary active transport molecules that accompany sodium in the **Na+ cotransports**?
**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
What is important to note about the Na+ H+ exchanger? (NHE)
it is NOT electrogenic
50
How many isoforms does the **Na+ H+ exchanger** have?
5 - 12 transmembrane region
51
Where is **NHE 1** located?
general (basolateral membrane)
52
Where is **NHE 3** located?
epithelial cells; apical membrane
53
Where is **NHE 5** located?
brain testis
54
Draw a schematic representation of the mechanism of which neurotransmitter are uptook by synaptic vesicles
55
What cation do **vesicular neurotransmitter antiporters** use?
**H+** they are proton antiports also called vesicular membrane antiporters (VMAT)
56
Where is **VMAT1** located?
brain neuroendicrine cells cholinergic synapses
57
Where is **VMAT2** located?
neurons adrenal chromaffin cells
58
Where is **VAChT** located?
cholinergic synapses
59
What are **vesicular neurotransmitter antiporters** inhibited by?
H+ ionophores
60
How many transmembrane segments do vesicular neurotransmitter antiporters have?
12 ## Footnote broad selectivity: E, NE, DOP, SER
61
What do **ABC transporters** bind?
1. AA 2. Peptides 3. Ions 4. Lipids 5. Bile acids 6. drugs
62
What is the mechanism of the **ABC transporter**? What are they dependent on?
transports against the concentration gradient ## Footnote **ATP**
63
Where are **ABC transporters** present?
plasma membrae endoplasmic reticulum mitochondrial membrane
64
What is an example of a important **ABC transporter**? What can happen if a mutation occurrs?
**CFTR** transporter - Cl- channel if a mutation occurrs cystic fibrosis may be the outcome
65
What are the **families** of the **ABC transporter**?
ABCA ABCB ABCC and further subfamilies
66
What is the function of the **ABCA1 family**?
cholesterol, phospholipid transport reverse cholesterol transport
67
What is the function of the **ABCA3** transporter?
translocation of pulmonary surfactant lipids mutation: respiratory distress szindroma
68
What is the function of the **ABCB1** (MDR1, multidrug resistance transporter)
transport of lipophylic compounds→ protection against toxins increased expression in tumor cells: drug resistance
69
What is the function of **ABCB4 transporter**? Where are they located?
Function: bile acid, phospholipid transport into bile Location: canalicular membrane of hepatocytes
70
**ABCC1 transporter**
phospholipids glutathione conjugates anti-tumor drugs
71
CFTR
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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