LECTURE 17 - PHOSPHOLIPIDS

Question 1

what are the different types of phospholipids?

Answer 1

phosphatidylcholine
phosphatidylethanolamine
phosphatidylserine
phosphatidylthreonine
phosphatidylinositol
phosphatidylglycerol

Question 2

what is the structure of sphingomyelin (a sphingolipid)?

Answer 2

sphingolipids contain an amide bond between the sphingosine and the phosphate

Question 3

what is the structure of glycolipids?

Answer 3

cerebrosides and gangliosides

Question 4

what is the structure of sterols?

Answer 4

cholesterol and derivatives

Question 5

what are the different fatty acids?

Answer 5

palmitate, oleate, sphingosine and stearate?

Question 6

what are the roles of membrane lipids?

Answer 6

maintain in/out asymmetry of the membrane
create microdomains
signaling

Question 7

how is in/out asymmetry of the membrane maintained?

Answer 7

flippase flips phospholipids inward
floppase flips phospholipids outwards
scramblase does both

Question 8

what are the microdomains of the membrane?

Answer 8

RAFTS:
gangliosides
sphingomyelin
cholesterol
thick and stiff
NON RAFTS:
glycerophospholipids (PC, PS, PE)
thin and fluid
made of shorter and unsaturated chains

Question 9

where does phospholipid synthesis happen?

Answer 9

in the ER

Question 10

what are the steps of synthesis of glycerophospholipids:PI, PG, cardiolipin

Answer 10

step 1.
activation of phosphatidic acid by CTP
this releases CDP-diacylglycerol and PPi
the PPi reaction with pyrophosphatase is what drives this reaction forward
step 2.
adding inositol to make phosphatidylinositol or glycerol3P to make cardiolipin

the take home message is that you need a high energy intermediate before you can add the necessary stuffq

Question 11

what is the kennedy pathway to make PE and PC

Answer 11

happens in all cell types
1. prime the head group with ATP
2. activate the head group
3. add the diacylglycerol
this pathway is special because you activate the head group instead of the phospholipid, but the concept of a high energy intermediate is still there

Question 12

what is the one carbon pathway to have the PE to PC conversion?

Answer 12

happens in the liver ONLY
the enzyme is PEMT: phosphatidylethanolamine methyltransferase
this pathway represents 30% of the PC production in the liver
step 1:
add the methyl group
step 2:
repeat
step 3:
repeat
PC has three more methyl groups than PE

Question 13

where does the added methyl come from in the one methyl pathway?

Answer 13

methionine is activated with ATP
this creates S-Adenosyl-L-methionine
this is a methyl donor molecule, a high energy intermediate

Question 14

which function of the liver depends on PC production?

Answer 14

to make bile, you need a perfect ratio between cholesterol, bile salts and PC
if there is too much of one, the bile crystallizes and you get gallstones

Question 15

how do the PE->PS and the PS->PE conversions happen?

Answer 15

PE->PS
phosphatidylethanolamine serine transferase

PS-> PE
phosphatidylserine decarboxylase

not a reversible enzyme but two separate ones
the CO2 is the difference between the two molecules

Question 16

how are sphingolipids made?

Answer 16

1. add an activated acyl to the serine backbone (palmitoyl CoA is the high energy intermediate)
   2a. transfer a phosphocholine head group from PC to make sphingomyelin
   2b. add a glucose head group from UDP glucose (high energy intermediate) to make cerebroside

Question 17

where are phospholipases located?

Answer 17

they are present in the plasma membrane

Question 18

what are the functions of phospholipases?

Answer 18

cleave phospholipids to:
generate signaling molecules
convert phospholipids
modulate the shape of the plasma membrane

Question 19

what do the different phospholipases create from a phospholipid?

Answer 19

phospholipase A1: lysophospholipid
phospholipase C: diacylglycerol
phospholipase D: phosphatidic acid

Question 20

what diseases are associated with phospholipase defficiency?

Answer 20

for example deficiency in sphingomyelinase causes Nieman-Pick Type A/B disease

Question 21

what is the Land’s cycle?

Answer 21

phospholipid is cut into lysophospholipid by phospholipase A, this also releases a free fatty acid
lysophospholipid is converted back by lysophospholipid acyltransferase which takes a fatty acid from Acyl-CoA

Question 22

how do lysophospholipids change the shape of the membrane?

Answer 22

create some curvature
this can be used for invagination and exvagination