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physiology and pharma > L3 - Transporters > Flashcards

L3 - Transporters Flashcards

1
Q

define passive diffusion

A

movement of molecules from region of high concentration to low concentration across a membrane

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2
Q

what type of molecules can passively diffuse? give examples

A

small
uncharged
non polar
lipid soluble

O2, CO2, glycerol, ethanol

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3
Q

fucntion of transmembrane proteins

A

form transporters or ion channels that allow movement of large / polar molecules across membrane

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4
Q

function of ion channels

A

act like a pore to allow passive diffusion of specific ions through the membrane

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5
Q

define facilitated diffusion

A

passive diffusion of molecules facilitated by a protein eg ion channel

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6
Q

define primary active transport

A

using a carrier protein (transporter) and energy provided from conversion of ATP to ADP +Pi (via ATPase) to transport a molecule across a membrane against its conc gradient

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7
Q

example of primary active transporter

A

Na / K / ATPase pump

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8
Q

define secondary active transport

A

uses energy from the flow of ions down a concentration gradient to co-transport another molecule against its conc gradient across a membrane

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9
Q

what are the two types of secondary active transport

A

symport (cotransport) -> molecule transported in same direction as ion providing the energy

antiport -> molecule transported in opposite direction to ion providing the energy

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10
Q

list the 3 functional types of transporter

A
  1. transporters that maintain ion gradients (ion transporters and pumps)
  2. nutrient / metabolite transporters
  3. NT transporters
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11
Q

why is NT re-uptake from the synaptic cleft important?

A
  • prevent new unwanted AP generation

- synapse would become refractory/inactivated due to receptor desensitisation if NT wasnt removed

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12
Q

how are NT removed from cleft

A
  1. passive diffusion into surrounding neurones
  2. degradation by enymes
  3. reuptake into terminal or astrocytes
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13
Q

what are the two types of plasma membrane transporter superfamilies

A
  1. Na+ / Cl- dependant transporters

2. Na+ /K+ dependant transporters

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14
Q

how many TMDs do the Na+ / Cl- dependant transporters have

A

12

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15
Q

are the N and C terimnals of the Na+ / Cl- dependant transporter intra/extra cellular?

A

both intracellular

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16
Q

describe structure of Na+ / Cl- dependant transporter superfamily

A

→ 12 transmembrane (H.phobic) domains

→ intracellular N & C terminal

→ extracellular loop between TMD 3&4 which contains 2-4 glycosylation sites

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17
Q

give examples of transporters that are Na+ / Cl- dependant

A 
SERT
NET
DAT
GABA transporter
Glycine transporter
choline transporter
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18
Q

list the types of glutamate transporters

A

EAAT 1-5

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19
Q 
where is 
EAAT1 
EAAT2 
EAAT3
EAAT4
EAAT5
found
A

EAAT1 -> glial cells
EAAT2 -> glial and neuronal cells
EAAT3 &4 -> neuronal cells
EAAT5 -> retina

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20
Q

how many TMDs do the Na+/K+ dependant transporters have

A

6-10 Hphobic

21
Q

example of a Na+/K+ dependant transporter

A

EAAT (glutamate and aspartate transporter)

22
Q

what is an electroneutral transporter and give an example

A

a transporter that doesnt change the electrochemical portetial of a cell (moves same number of + / - in and out)

SERT

23
Q

what is an electrogenic transporter and give an example

A

a transporter that changed the electrochemical potential of a cell (moves an odd number of + / - in or out of the cell)
glutamate EAAT

24
Q

where else is EAAT3 expressed other than glutamate neurones and why

A

GABAergic neurones as glutamate is the precursor for GABA

25
Q

why is glutamate re-uptake into glial cells more energy efficient?

A

requires less energy because there is a smaller concentration gradient of Glutamate in the glial cell compared to the nerve terminal
due to conversion of glutamate to glutamine in glial cells

26
Q

describe the glutamate - glutamine shuttle process

A
  1. glutamate taken into glial cell by EATT1/2 where its converted to glutamine by glutamine synthase
  2. glutamine leaves glial cell via N amino acid transporter
  3. glutamine transported into neurone by A amino acid transporter
  4. glutaminase converts glutamine back into glutamate in the nerve terminal
  5. glutamate packaged into vesicle
27
Q

what ion is used to co transport in the A and N amino acid transprters?

A

Na

28
Q

describe calcium independant NT release

A

reverse transport -> when transporters work in reverse and move NT into the cleft rather than into nerve terminal

29
Q

what enzymes convert
glutamate -> glutamine
glutamine -> glutamate

A

glutamine synthase

glutaminase

30
Q

what GABA transporters are found on the membranes of astrocytes

A

GAT-2

GAT-3

31
Q

what is believed to cause reverse transport of NTs?

A

the Na gradient that usually co-transports the NT in.
if intracellular Na gets too high it may move in the opposite direction into the cleft (via the transporter) taking NT with it

32
Q

what does packaging NT into vesicles prevent

A
  • leakage into cleft
  • NT metabolism in the terminal
  • toxicity to neurone
33
Q 
name the 
monoamine 
ACh 
GABA/Glycine 
Glutamate transporters
A

VMAT (1&2)
VAchT
VIAAT (vesicular inhibitory amino acid transporter)
V-glut 1, 2, 3

34
Q

what does VMAT transport

A

serotonin
dopamine
NA
histamine

35
Q

what does VMAT transport

A

serotonin
dopamine
NA
histamine

36
Q

where is
VMAT1
VMAT2 expressed

A

endocrine cells

neurones

37
Q

what is a difference between the vesicular and plasma membrane glutamate transporters?

A

the membrane transporter transports aspartate and glutamate, the vesicular can only transport glutamate

38
Q

describe structure of the VMAT and VAchT transporters

A
  • 12 TMDs
  • large Hphilic loop with 3-5 potential glycosylation sites between TMD 1&2 (in vesicle lumen)
  • N and C terminal is in cytoplasm of nerve terminal
39
Q

describe structure of VIAAT

A
  • 10 TMDs
  • Long N terminal and short C terminal, both in cytoplasm of nerve terminal
  • large loop between TMD 1&2 (inside vesicle)
40
Q

describe significance of glutamate transporters in epilepsy

A
  • knockout mice for the equivalent EAAT2 transporter experienced seizures
41
Q

name the GABA plasma membrane transporter

A

GAT

42
Q

describe the mechanism of anti-epileptic drug tiagibine

A
  1. it is a GABA transporter blocker - prevents re-uptake of GABA into nerve terminal
  2. increases [GABA] in cleft and so increases receptor binding
  3. increased inhibition
43
Q

list diseases that can be treated by interfering with transporters (and which transporters)

A
  1. Epilepsy -> GAT blockers
  2. ADHD -> DAT blockers
  3. Depression -> NA / 5-HT (NET / SERT) blockers
44
Q

describe the mechanism of action of fenfluramine (anti-obesity drug) in regards to the serotonin transporter

A

causes SERT to work in reverse, depositing 5-HT into the cleft instead of re-uptaking it (reverse transport)
also disrupts vesicle storage

45
Q

wwhat effect will blocking VMAT and other vesicle transporters have?

A

reduce [NT] in the cleft, as less can be exocytosed

46
Q

describe significance of reverse transport in ischemia

A

reverse tsport of plasma membrane glutamate transporters occurs in ischemia, which results in increased [glutamate] in cleft causing excitotoxicty

47
Q

where does cocaine act?

A

SERT, DAT, NET

inhibiting reuptake

48
Q

where does amphetamine act?

A

DAT, SERT, NET clocking reuptake

also causes DAT reverse transport

49
Q

where does MDMA act?

A

SERT, where it blocks reuptake and promotes reverse transport
MDMA has higher affinity for SERT than serotonin itself

physiology and pharma (18 decks)

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