Lipids (Lecture 18)

Question 1

where are phospholipids synthesized?

Answer 1

endoplasmic reticulum

Question 2

what kind of pathways is PL synthesis?

Answer 2

anabolic pathway

build a more complex molecule needs an input of energy

Question 3

steps in phospholipid synthesis (PI, PG, Cardiolipin)

Answer 3

starting from phosphatidic acid…

1. activation of phosphatidic acid. this is done by combining CTP with phosphatidic acid to produce CDP-diacylglycerol. PPi is released and this generates 2Pi (- delta G, releases energy–> couples this energy to drive reaction)

this reaction is favourable and irreversible

the enzyme involved is CDP-diacylglycerol synthase

2. the high energy intermediate has inositol (generates phosphatidylinositol, PI) or glycerol 3P (generates phosphoatidylglycerol, PG)
   (3) with the enzyme cardiolipin synthase, 2PG will be combined to make cardiolipin

Question 4

what is the Kennedy pathway

Answer 4

synthesis of the PE, PC

1. prime the head group with ATP (raise internal energy to generate molecule of higher order)
   ethanol amine/choline –> phospho-ehtanolamine/choline (via kinase)
2. activation of. head groups. this is done by adding CDP and releasing PPi with a cytidyltransferase.
3. add DAG and release DAG to produce PC or PE.

Question 5

what is the PEMT pathway?

Answer 5

another way to synthesize PC from PE.

only in liver (30% of total PC)

1. adding methyl group to PE
2. repeat
3. repeat to generate PC.

phosphatidylethanolamine methyltransferase is the enzyme responsible for these methylations.

Question 6

in the synthesis of PC, where do the carbons that methylate PE come from?

Answer 6

one carbon pathway

add methionine to ATP

add adenosyl group to release PPi

this generates a sulfonium moiety. the solfonium allows the methyl group to detach (unstable)

Ado-Met donated the methyl groups

Question 7

which function is highly dependent on abundant PC production in the liver?

Answer 7

PC is an important component of bile. bile contains a lot of cholesterol, PC and bile salts and without proper regulation, this may lead to gull stones.

Question 8

identify a high energy intermediate in the PEMT-mediated conversion of PE to PC

Answer 8

Ado-Met (via the hydrolysis of PPi)

Question 9

what phenotype is observed in cases of PEMT deficiency? and what it the mechanism?

Answer 9

gull stones, fatty liver:

accumulation of PE that cannot be converted into PC

accumulation of triglycerides

Question 10

how does PE convert to PS?

Answer 10

a serine is added to PE via PE serine transferase

Question 11

how does PS convert to PE?

Answer 11

PS removes the CO group via phosphatidylserine carboxylase. CO2 is removed.

Question 12

what is the mechanism for the synthesis of sphingolipids?

Answer 12

1. adding and activated acyl (palmitoyl-acyl) to the serine backbone.
2. fatty acyl-coa generates ceramide
3. a. transferring of a PC head group to ceramide to make the sphingolipids
4. b. addition of UDP-glucose to ceramide to generate cerebroside.

Question 13

what is phospholipase responsible for?

Answer 13

cleave phospholipids to generate signalling molecules, convert phospholipids and to modulate the shape of the plasma membrane

Question 14

what are phospholipase deficiencies associated with?

Answer 14

disease

deficiency in sphingomyelinase causes Nieman-Pick type A/B (issues wit endocytosis of lipoproteins because of the maturation of the endosomes)

Question 15

what is the mechanism for Land’s cycle?

Answer 15

phospholipase A2 generates lysophospholipids, while releasing a fatty acid.

the lysophospholipid is the substrate for the generation of other phospholipids, when Acyl-CoA is added via lysophospholipid acyltransferase

Question 16

what induces modifications to the structure/shape of the plasma membrane?

Answer 16

the shape of then phospholipids

for endocytosis, the membrane must invaginate by converting cylindrical PL into cone PL. this is done via the removal of a couple of PL.