Lipids (Lecture 17)

Question 1

Exogenous pathway of triglycerides. (4)

Answer 1

-synthesized/injested
-transported
-stored
mobilized to generate energy

Question 2

Triglyceride Journey for energy production (5)

Answer 2

ENDOGENOUS
- tryacylglycerols are synthesized in the liver
-triacylglycerols are transported through the bloodstream via VDLs
EXOGENOUS
–small intestine contains hydrolytic enzymes in the pancreas
-tryacylglycerols are transported through the lymph/blood via chylomicrons

-free fatty acids are transported and bound to serum albumin

Question 3

What does pancreatic lipase do?

Answer 3

pancreatic lipas eis an enzyme synthesized/secreted by the pancreas. when in contact with the micelles, pancreatic lipase will digest the tryacylglycerols into free FAs and monoglycerides.

Question 4

When does lipolysis occur?

Answer 4

fed state (during/ after a meal)

Question 5

What does lipoprotein lipase do?

Answer 5

LPL is found in the blood vessels and it will digest the triglycerides within the reconstructed chylomicron into free FAs and monoglycerides. This allows FAs to be taken up by adipose tissue and muscle cells.

Question 6

How do adipose tissue and muscle cells store FAs?

Answer 6

lipid droplets stores triglycerides

Question 7

Why are there many reactions of synthesis and degradation of lipids?

Answer 7

this is due to the lipids hydrophobic nature. the lipids cannot be transported well without both lipolysis and lipogenesis.

Question 8

What is the mechanism of lipoprotein lipase. (LPL)?

Answer 8

this occurs in the fed state

the chylomicrons in the blood will diffuse to reach the tissue/cell targets (either the muscle cell or adipose tissue)

the LPL meet the chylomicrons in the blood vessel and the blood vessels of the endothelial cells that coat the muscles and adipose tissues. the LPL will convert triglycerides into a monoglyceride and free fatty acids, so that it can be taken up by the cells.

within the cells, the fatty acids will be reassembled into triglycerides.

this process is lipolysis

Question 9

what occurs after the reassembly of triglycerides?

Answer 9

the triglycerides are stored in the form of fatty acids

Question 10

during exercise, how are lipids used?

Answer 10

1. use stored ATP
2. creatine phosphate (p-creatine+ ADP -> creatine +ATP via creatine kinase)
3. anaerobic glycolysis
4. generation of ATP via aerobic glycolysis

once the pool of glycogen and glucose is exhausted, fat is burned and the stored lipids droplets, thus triglycerides are broken down

Question 11

How do the structures of lipids droplets vary?

Answer 11

in adipocytes:
the adipose cell is a specialized cell that functions to store neutral lipids.
the adipocytes store large amounts of triacylglyerols as fat droplets that nearly fill the entire cell.
the nucleus and mitochondria and squeezed in the side of the membrane

lipid droplets in liver:
smaller lipid droplets that serve as transient buffer reservoir of esterified fatty acids and esterified cholesterol.

Question 12

when does lipolysis occur and what is it?

Answer 12

it occurs in states of fasting or during exercise

it is the breakdown of triglycerides

Question 13

mechanism of lipolysis of lipid droplets

Answer 13

3 reactions

TAG (adipose trigliceride lipase)
DAG (hormone sensitive lipase)
MAG (monoacylglycerol lipase)

Question 14

what happens after lipolysis of the lipid droplet int he adipose tissue?

Answer 14

the free fatty acids (3) will be transported into the bloodstream and bound to albumin (amphipathic protein with a hydrophobic pocket). 
this will deliver the free fatty acids to the muscle to use as a source of ATP  
the glycerol (sugar) is soluble in blood and not bound 
glycerol can also be broken down

Question 15

how is lipolysis controlled?

Answer 15

lipolysis is con trolled via the hormonal regulation of PKA (protein kinase A)

Question 16

what does PKA do in lipolysis and how does it do this ?

Answer 16

PKA phosphorylates perilipin and HSL (hormone sensitive lipase)

adrenaline binds to the beta adrenergic receptor and G-alpha then associates to adenyl cyclase to produce cAMP. the cAMP will activate PKA and phosphorylates compounds.

Question 17

what is perilipin?

Answer 17

protein that coats the surface of the lipid vesicles (amphipathic).

it has alpha hydrophobic residues that interact with the core of the lipid droplets.

Question 18

what is the purpose of phosphorylating perilipin?

Answer 18

when PKA phosphorylates perilipin, it allows HSL to access the pool of triglycerides in the cell.

perilipin modifies the structure of the lipid droplet to allow HSL to interact with the core of the lipid core.

finally, this results in the hydrolysis of DAG.

Question 19

what are the 2 ways of lipolysing triglycerides?

Answer 19

1. after a meal via pancreatic lipase
   and/or lipoprotein lipase in the fed state. (storage)
2. mobilize energy by breaking down the stage lipid droplets. this is done through hormone regulation, as for when exercise is initiated, adrenaline binds to the receptor, which causes a cascade of events , eventually activating PKA to phosphorylate perilipin and HSL.

Question 20

where does lipogenesis occur?

Answer 20

in the enterocytes, the re-synthesis of triglycerides to secrete in the form of chylomicrons into the blood

more specifically, this is done in a hydrophobic area between two membrane layers within the endoplasmic reticulum (since they are neutral lipids)

it will then bud from the membranes and form a lipoprotein (chylomicron)

Question 21

what are the 2 steps involved in triacylglycerol re-synthesis?

Answer 21

1. activation by CoA via Acyl-CoA synthetase

the FA from uptake uses the energy from ATP to couple it to the CoA to generate an acyl CoA. this generates and intermediate. in 2 steps, another CoA group attaches via the same enzyme to make Acyl CoA. note that the formation of inorganic pyrophosphate provides the energy to make the intermediate compound.

2. the 2-monoacylglycerol (via MGAT enzyme) pathway to generate diacylglycerol (DAG) and then DGAT to synthesize a triacylglycerol

Question 22

in step 1, why do we ass a CoA onto the FA (activate it) ? (2 reasons)

Answer 22

to make a high energy intermediate to make the second part of the make reassembly favourable

trap fatty acids

Question 23

Lipogenesis De Novo steps

Answer 23

(liver/ adipose tissue)

1. generate glycerol-3-phosphate via DHAP synthesis or phosphorylation of glycerol.

adipocytes lack glycerol kinases, thus the phosphorylation of glycerol only occurs in the liver.

2. add acyl CoA to generate phosphatidic acid (2 acyl chains)

AT THIS POINT IT PHOSPHATIDIC ACID COULD BE USED FOR PHOSPHOLIPID SYNTHESIS OR FOR THE SYNTHESIS OF TRIACYLGLYCEROL

3. dephosphorylation via lipid (regulatory enzyme). it is the control enzyme that decides if it produces TAG or PL. lipid is regulated at the transcriptional level.
4. add acyl-CoA via DGAT to make treacly glycerol

Question 24

what regulates lipogenesis?

Answer 24

insulin also manages lipogenesis in adipose tissue and the liver

Question 25

what does insulin do and how?

Answer 25

insulin regulates lipogenesis.

when bound to its receptor, a cascade of events is initiated, which leads to the synthesis of all of the enzymes required for the synthesis of TAG

this is transcriptional control

Question 26

what occurs in the fed state

Answer 26

lipolysis (pancreatic lipase)

reassembly

transport via chylomicrons into the blood

lipolysis via lipoprotein lipase

lipogenesis in the lipid droplets

(stimulated by insulin)

Question 27

what occurs in a fasting/exercise state?

Answer 27

lipolysis in the lipid droplets (stimulated by adrenaline)

transport via albumin into the blood

uptake in tissue

beta oxidation to generate ATP

Question 28

what do flippase, floppase and scamblase

Answer 28

proteins that modulate the balance of lipid distribution within the membranes

Question 29

what is found on the inner side of the cell’s surface membrane and why?

Answer 29

phosphatidylserine

phosphatidylethanolamine

because they induce signal transductions

Question 30

what is found non the outer membrane of cell surfaces and ?

Answer 30

phosphatidylcholine and sphingomyelin

Question 31

what are calveolae?

Answer 31

coated raft micro-domains

rafts can assemble and form invaginations

this allows for the assembling of signalling complexes and provides elasticity to the membranes.

Question 32

what is the function of Rafts?

Answer 32

partitioning (sequesters) of receptors / effectors into different domains could modulate signalling

depleting the cell of sphingomyelin or cholesterol will decrease the rafts, which in turn will not permit signalling due to structure modifications.

Question 33

caveolae function?

Answer 33

has structural function where it can serve as a buffer for the plasma membrane. (copes with compression or stretching of the plasma membrane)