L18 Phospholipids

Question 1

TF: lipid droplets are in the plasma while lipoproteins are in the cells

Answer 1

False, it is the opposite

lipid droplets are found in the cell while lipoproteins are found in the plasma

Question 2

Under which metabolic circumstances would TG synthesis be favoured?

A. When cells are dividing
B. To maintain membrane rafts balance
C. After a fatty meal
D. When fasting for > 12h
E. In case of stress, to provide signaling molecules

Answer 2

C

Question 3

What are the 3 kinds of membrane lipids

Answer 3

phospholipids, glycolipids, sterols (cholesterol)

Question 4

How are the structures of glycerophospholipids (phospholipids) and sphingolipids different

Answer 4

main difference is the backbone; sphingolipids have a sphingosine backbone while glycerophospholipids have a glycerol backbone

sphingolipids: sphingosine (long chain amino alcohol) backbone + 1 FA chain + polar head group

glycerophospholipids: glycerol backbone + 2 FA chains + phosphate group + polar head group

Question 5

TF: all glycerophospholipids have the same polar head and FA chains

Answer 5

False, they can have different kinds of polar heads and different kinds of FA chains

Question 6

What are the roles of membrane lipids? (3)

Answer 6

1. in/out asymmetry (leaflet asymmetry essential for function)
2. microdomains (RAFTs vs NON-RAFTs)
3. Signaling (PI, PIP3, PIP2, IP3)

Question 7

What is the difference between a RAFT and NON-RAFT domain?

Answer 7

RAFT: thick and stiff (sphingomyelin, cholesterol, other)

NON-RAFT: thin and fluid (glycerophospholipids)

Question 8

What is sphingomyelin and how is it different from sphingolipids

Answer 8

sphingomyelin is a sphingolipid that is more similar to phospholipids as it has a phosphate and choline group (polar)

Question 9

Under which metabolic circumstances should PL synthesis be favoured? (choose all that apply)

A. In case of stress, to provide signaling molecules
B. After a fatty meal
C. When fasting for > 12h
D. To maintain membrane rafts balance
E. When cells are dividing

Answer 9

A, D, E

Question 10

Where can phospholipids be found INSIDE the cell

Answer 10

endoplasmic reticulum (ER)

phospholipid and neutral lipid biosynthesis

Question 11

Why are there so many kinds of glycerophospholipids

Answer 11

to aid in membrane fluidity (under conditions of temperature change for example), signaling, other housekeeping roles

Question 12

TF: RAFT domains have more double bonds in their FA chains than NON-RAFT domains

Answer 12

False, non-raft domains have more double bonds and thus are more fluid

Question 13

TF: Longer FA chains in the plasma membrane increases fluidity

Answer 13

false, short FA chains result in increased fluidity of the plasma membrane

Question 14

How are PI, PG, and Cardiolipin synthesized?

Answer 14

1. Activate Phosphatidic acid using CTP to generate high energy intermediate, 2Pi released drive the reaction forward and make it irreversible
2. PI = add inositol to intermediate
   PG = add glycerol-3-phosphate
   Cardiolipin = 2PG + Cardiolipin synthase (release 1 glycerol)

Question 15

TF: Kennedy pathway occurs in all cell types

Answer 15

True

Question 16

Explain the Kennedy pathway and what it produces

Answer 16

Kennedy pathway produces PE and PC (phospholipids)

We start with ethanolamine or choline and invest 1 ATP to prime the head group

Then, 1 CTP is invested to make a high energy intermediate by activating the head group

Polar head group is then added to diacylglycerol to make PE (if starting with ethanolamine) or PC (if starting with choline)

Question 17

What is the difference between [PI, PG, Cardiolipin] synthesis and [PE, PC] synthesis? What do they have in common?

Answer 17

PI, PG, Cardiolipin pathway activates the phosphatidic acid while PE, PC pathway (Kennedy pathway) activates the head group

They both generate a high energy intermediate

Question 18

How does PE->PC and what is the significance of this?

Answer 18

It transforms PE -> PC by adding 3 methyl groups to PE: this is done by PEMT

*the methyl comes from 5-adenosyl-L-methionine

This pathway produces 30% of PC in liver and is only present in the liver

Question 19

What is the one carbon pathway? What happens

Answer 19

Methionine interacts with ATP to generate 5-adenosyl-L-methionine. Within the structure of 5-adenosyl-L-methionine, there is a highly unstable soulful group (sulfonium) thereby making it a very good 1 carbon donor

Question 20

Why are 2 pathways needed to synthesize PC? (Kennedy pathway and PE->PC PEMT conversion pathway)

Why is this regulation necessary

Answer 20

Abundant PC production is needed in the liver mainly for bile production (mainly composed of bile salts, cholesterol, PC)

Bile composition follows a tight ratio or else gallstones can be produced

Question 21

What symptom is observed if you have PEMT deficiency?

Answer 21

Gallstones

Question 22

What is the high energy intermediate in the PEMT pathway?

Answer 22

5-adenosyl-L-methionine

Question 23

List the kinds of glycerophospholipids (6)

Answer 23

PI, PG, Cardiolipin, PE, PC, PS

Question 24

How is PE transformed into PS? What about the other way around?

Answer 24

PE->PS = transferase (ethanolamine group is replaced by serine group)
PS->PE = decarboxylase (lose 1 CO2)

Question 25

How are sphingosines synthesized?

Answer 25

An activated acyl - Fatty-acyl-CoA (from FA - serine - and CoA - palmitoyl-CoA - reaction) is added to a serine backbone thus making ceramide

Ceramide can interact with either PC resulting in sphingomyelin or UDP-glucose resulting in cerebroside (glycosphingolipid)

Question 26

What are phospholipases, what do they do, and where are they located

Answer 26

They are enzymes that will remodel lipids by acting on the existing phospholipids at specific sites

Cleave phospholipids to: generate signalling molecules, convert phospholipids (Lands’ Cycle), modulate plasma membrane shape

Mostly located on plasma membrane

Question 27

What is an example of a phospholipase for signalling?

Answer 27

PLC where the g-alpha-q activates PLC which will act on PIP2 to generate IP3 (and DAG) for secondary messenger effects

Question 28

What is CDP

Answer 28

It acts as an active carrier and plays a role in glycerophospholipids synthesis (activation of high energy intermediates)