Membrane Proteins Flashcards

1
Q

why do we need membranes?

A
  • seperate extracellular env from intracellular contents
  • in cell: organelles contents are seperated
  • we need gradients of chemicals -> creates energy
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2
Q

what is plasma membrane permeable / impermeable to?

A
  • *permeable**:
  • gases
  • small uncharged polar molecules
  • *unpermeable**:
  • large uncharged polar molecules
  • ions
  • charged polar molecules
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3
Q

describe the concentration uptake relationship for glucose and oxygen for simple diffusion and plasma membrane (with and without transport proteins)

A

oxygen: simple diffusion: passes through membrane easily: non saturable

glucose without transport: simple diffusion slow uptake bc glucose is relatively impermeable: non saturable

glucose with transport: at low glucose concentration - rate of uptake increases quickly, but then slows down/ there is a limit to rate of glucose uptake into cell saturatable kinetics

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4
Q

what is Vmax?

what is 1/2Vmax used for?

A

Vmax: The rate of reaction when the enzyme is saturated with substrate is the maximum rate of reaction

1/2Vmax: used to compare different proteins and how efficient they are at taking up glucose. gives us a way of comparing uptake constant (Km)

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5
Q

what is determines how selectively permeable a membrane is?

what % of the coding capacity of human genome is for membrane proteins?

A
  • the protein component of the membrane
  • 26% of coding capacity of the human genome is for membrane proteins
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6
Q

what poses a problem with membrane proteins?

how get over this?

A

membrane proteins have to have someway of inserting themselves into the protein, whilst also having regions that are inside or outside of the membrane:

have to function in:

- lipid bilayer environment: hydrophobic

- hydrophilic environment that exists outside bilayer

solution: specialised domains that allow them to be inserted within the membrane

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7
Q

how do different membrane proteins interact with a cell membranes? (5)

A
  • alpha helix (1 & 2)
  • rolled up beta sheet (3) - forms a pore
  • amphiphilic alpha helix (contains both hydrophilic and phobic components - 4)
  • lipid anchors (5 & 6)
  • non covalent interation with a bona fide membrane protein (brings them v close to membrane, 7&8)
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8
Q

what are the five different membrane proteins? (5) explain their functions

A
  1. channel proteins - move with concentration gradient
  2. transporter proteins: move against concentration gradient. requires ATP
  3. allow cell to cell interaction - link to cytoskeleton / ECM
  4. receptors: transmission of signals across the membrane
  5. enzymes
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9
Q

most eukaroytic cells membrane proteins that cross the membranes are what structure?

A

alpha helices

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10
Q
  • transmembrane alpha helices have what type of a.a. within the plasma membrane?
  • how can one protein’s structure differ due to the differing environment across extracellular, within lipid bilayer and then within the cytosol?
A

- lipid bilayer - they have non-polar amino acids in the hydrophboic core of bilayer

- inside cytosol: reducing environment (dont get disulphide bonds)

- extracellular space: oxidising environment (get disulphide bonds). post translational modifcations mean get glycosylated

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11
Q

how does the cell protect itself from a hostile extracellular environment?

A
  • glycoproteins and glycolipids form a protective carbohydrate layer
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12
Q
  • describe the movements of membrane proteins (within the membrane)

(- what can lipid-anchored membrane proteins do?)

A
  • can diffuse laterally
  • change conformation
  • be internalised and recycled

(lipid membrane proteins: can associate / dissociate from the membrane)

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13
Q
  • describe how channel proteins allow passive movements of solutes through membranes
A
  • channel protein can open / close. (can depend on voltage).
  • allows passive flux, from high concentration to a low concentration of solutes
  • regulated and selective by selectivity filter
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14
Q

how do transporters facilitate passive movement of solutes?

A
  • binding site for solute -> induces conformational change = exposes solute to other side
  • only works down hill - from high concetration to low concetration / passive movement
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15
Q

what is the net flux of active transport of a substrate dependent on?

A

on ATP for the primary active pump

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16
Q

apart from concentration gradients, what can some membrane proteins use to transport substrates?

where often found?

A

electrochemical gradients

e.g: electrochemical gradient for Na+ -> efflux of Na+ by N+/K+ ATPase pump c.f. -ve charge on inner leaflet pump

17
Q

explain process of secondary active transport

A

( membrane proteins can use co-transport ions (that uses an downhill electrochemical gradient) to transport a molecule agaisnt a solute concentration gradient)

  • In secondary active transport, the movement of the (sodium) ions down their gradient is coupled to the uphill transport of other substances by a shared carrier protein (a cotransporter).*
  • energy is released as the cotransported ion moves down its electrochemical gradient. the solute uses this energy of the electrochemical gradient to go agaisnt the concentration gradient
  • the direction of the electrochemical gradient can be the same (symport) or opposite (antiport) as the transported molecule
18
Q

name the differences betwen primary and secondary active transport

A

primary active transporter

  • uphill solute translocation
  • requires ATP hyrdolysis and release of energy
  • e.g. Na+ / K+ ATPase. effluxes Na+ to make a powerful gradient
  • (directly hydrolyses ATP)

secondary active transporter:

  • uphill solute translocation is possible if coupled to downhill movement of an ion –(uses the electrochemical gradient)
19
Q
A
20
Q

explain how glucose is absorbed from intestinal lumen into portal vein

A

aim: transport glucose from intestinal lumen -> portal vein

1. primary active transport: Na//K+ ATP pumps Na+ out of intestinal epithelial cell into portal vein. sets up electrochem. gradient.

2. secondary active transport: SGLT1 symporter brings glucose into the epithelium cell. Na+ and glucose transported (through 2ry AT) from the intestinal lumen into the intestinal epithelium.. (Na+ goes in and glucose goes along with it).

3. leads to high levels of glucose in intestinal epithelium. faciliated diffusion of glucose via Glut2 facilated diffusion transporter causes gluocse to move from intestinal epithelium into portal vein. (Glut 2 is only expressed on basal lateral membrane)

21
Q

what is bile made of?

A

(red text shows all the transporter and membrane proteins used in production of bile)

22
Q

what is cholestasis?

  • occurs from mutations in which proteins?
A

Cholestasis is reduction or stoppage of bile flow

  • occurs from mutations in transporters that produce bile (ABCB11 and ABCB4 transporters)
23
Q
A
24
Q

what is involved in healthy bile acid circulation ?

A

cycle of bile salts:

  • bile salts are formed in hepatocytes
  • bile salts are transported (Primary AT) from hepatocyte membrane into bile duct and stored in gall bladder
  • when released and in intestine, bile salts are transported across basolateral membrane back to hepatocyte (secondary AT)

= range of transporters used! !

25
Q

what is name of disease for failure of healthy bile acid cycle?

A

only need failure in ONE transporter (ATP8B1 in hepatocytes) cause this disease

progressive familial intrahepatic cholestasis (PFIC)

  • jaundice
  • dark urine
  • pruritis (severe itching)
  • foul smelling fatty stool

failure to thrive

  • nause / vomiting

need liver transplant .

26
Q

what channel causes cystic fibrosis?

A

- CFTR channel: chloride channel on the plasma membrane of epithelial cells.

  • phosphorylated by PKA and gated by ATP
  • not a pump! is a channel in the membrane
27
Q

how can you measure chloride flow through channel?

A

patch clamp technique - can measure movement of ions through channel

28
Q
A
29
Q

name and describe two mutations in CFTR protein that cause CF

what are the drugs used to treat / how work?

A

- mutant ΔF508 CFTR: no mature CFTR gets to the membrane. fails to get folded properly and gets degraded in ER. 85% cases

drug: Lumacaftor (drug class = corrector) helps ΔF508 to fold, so more channel molecules reach plasma membrane = chemical chaperone. CFTR becomes more stablilised

mutant G551D CTFR: channel fails to open properly

drug: Ivacaftor: (drug class = potentiator) assists in opening of the channel by binding directly to channel.

30
Q

describe the structure of epithelial cells with regards with different transporters in their basolateral and apical membranes

A

Epithelial cells are ‘polarised’ with different transporters on their basolateral and apical membranes to permit transport across the cell