Lecture 2.2

Question 1

Is the membrane bilayer symmetrical?

Answer 1

No

• Allows membrane function
• Asymmetric synthesis, specific lipid transport/translocation
• Minimal spontaneous flip-flop

Question 2

What phospholipid may act as a signal for apoptosis`?

Answer 2

Phosphatidylserine - by flip-flopping onto the outer PM leaflet

Question 3

Different membranes

Answer 3

Different lipid composition - allows each to be specialised for their function

Question 4

Lateral vs transverse lipid membrane movement

Answer 4

Lateral - fast
Transverse - very slow (flip-flop)

Question 5

Can lateral movement occur over large distances?

Answer 5

No, instead the lipid is moved through the cytoplasm

Question 6

Do fatty acid chains affect fluidity?

Answer 6

Saturated chains - interact strongly with other ones, reduce fluidity

Unsaturated chains - more fluid

Question 7

Flippases: what are they and what is an example?

Answer 7

Enzymes that use ATP to ‘flip’ lipids from the outer leaflet to the inner leaflet of a membrane

Aminophospholipid translocase - removed PS and PE from the outer leaflet to the inner leaflet, generating PM lipid asymmetry

Question 9

P4-ATPase: what is it, what does it do, and how is it activated?

Answer 9

Flippase

Flips

Binds with CDC50 which results in phosphorylation and it then moved from the ER to the PM where it can use ATP to ‘flip’ the lipid

Question 10

Floppases: what are they and what do they do?

Answer 10

ATP binding casette (ABC) transporters

Use ATP to ‘flop’ lipids from the inner leaflet to the outer leaflet

Question 11

Scramblases: what are they and why are they used?

Answer 11

Catalyse lipids in a bidirectional fashion without using energy

Question 12

Scramblases: how are they used in conjunction with flippases?

Answer 12

• High Ca2+ causes TMEM activation
• TMEM inactivates flippases and scrambles the membrane resulting in PS exposure - potential for cell death
• Once Ca2+ levels decrease TMEM becomes inactivated
• Flippases continue flipping PS, preventing cell death

Question 13

Lipid production review

Answer 13

ER -
Synthesis of glycerophospholipids (PC,PS,PE,PI)
Synthesis of ceramide (sphingomyelin & glycolipid precursor)

Cholesterol:
Synthesised in ER
Steep gradient of cholesterol across the secretory pathway - ER low, PM high

Golgi
Synthesis of Sphingo- & glycolipids

Sphingolipids/glycolipids are post-Golgi, outer leaflet components
Preferentially transported to PM, not present in ER
∴ Must be actively incorporated in to anterograde (forward) vesicles, and excluded from retrograde vesicles

Question 14

How do lipids move through organelles?

Answer 14

Lipid transport proteins

• Donor membrane docking - extraction - donor membrane undocking - diffusion - acceptor membrane docking - lipid deposition - acceptor membrane undocking - further diffusion

Question 15

TULIP proteins

Answer 15

An example of a lipid transport proteins

Contain a large hydrophobic tunnel that allows lipids to pass straight to organelles