Absorption and Transport of Dietary Fat

Question 1

Are lipids water soluble?

Answer 1

No. they are hydrophobic

Question 2

What defines a lipid?

Answer 2

It’s solubility properties, not its chemical structure

Question 3

What are some examples of lipids?

Answer 3

1) Fatty acids
2) Solid or liquid “fats” Triacylglycerols (TAG), triglycerides (TG)
3) Membrane phospholipids (phosphatidylcholine, sphingomyelin)
4) Cholesterol
5) Steroid hormones

Question 4

What is the composition of fatty acids?

Answer 4

they consist of a long hydrocarbon tail with a carboxylic acid head region

Question 5

How many fatty acyl groups does glycerol have?

Answer 5

3

Question 6

What are the major source of dietary fatty acids (FA)?

Answer 6

Triacylglycerols (TAG) a.k.a. triglycerides (TG)

Question 7

What are bile salts derived from?

Answer 7

cholesterol

Question 8

Describe the composition of bile salts

Answer 8

They do retain the cholesterol ring structure. They differ from cholesterol in that the rings in bile salts contain more hydroxyl groups (Has hydrophilic/’fatty’ side with –OH and hydrophobic side) and a polar side chain and lack a 5-6 double bond.

This makes it amphipathic!

Question 9

What is the difference between saturated and unsaturated fatty acids?

Answer 9

Saturated fatty acids have NO double bonds. Unsaturated fatty acids have interspersed double bonds.

Question 10

What is the function of oral and gastric lipases in relation to FAs?

Answer 10

function to knock off short chains of FAs from ingested TAGs

NOTE: do not effect long chain fatty acids

Question 11

How does Pancreatic lipase work?

Answer 11

It works on TAGs and removes FAs from positions 1 and 3, releasing 2 fatty acids and a 2-Monoacylglycerol.

Question 12

What does pancreatic lipase require to work?

Answer 12

Requires protein colipase to stabilize and localize lipase near the bile salt-TG particle

Question 13

How does protein colipase work?

Answer 13

it is an enzyme essential for the absorption of dietary long-chain triglyceride fatty acids.

Colipase is thought to anchor lipase noncovalently to the surface of lipid micelles, counteracting the destabilizing influence of intestinal bile salts. Using primers derived from the known amino acid sequence

Question 14

What is the role of Cholesterol esterase?

Answer 14

Cholesterol esterase breaks down cholesterol ester into FA and cholesterol.

Question 15

What does Phospholipase A2 do?

Answer 15

breaks down phospholipids into FAs and lysophospholipids

Question 16

Outline the steps in the digestion of TAG to the formation of chylomicrons

Answer 16

o TAG is ingested.
o Pancreas releases pancreatic lipase and colipase (and HCO3-). Gallbladder releases bilesalts
into lumen of small intestine.
o Bile salts surround TAG.
o Colipase (no enzymatic activity) binds to bile salts. This attracts pancreatic lipase to TAG.
o Pancreatic lipase breaks down TAG into fatty acids and 2-monoacylglycerol
o Fatty acids and 2-MG are absorbed into intestinal epithelial cells from the lumen
(because there is no TAG transporter)
o Inside cell, Fatty acids are “activated” with ATP and Coenzyme A to become FA-CoA.
o Fa-CoA is esterified to 2-MG to form Diacylglycerol.
o Diacylglycerol reacts with a second Fa-CoA to produce TAG.
o The TAGs are packaged into chylomicrons by ApoB48 and microsomal TG transfer protein starting in the lumen of the rough ER.
o An immature chylomicron is formed as it moves through the ER and Golgi, and it is released into the lymph.
o The chylomicron gets transported into the blood where it becomes mature.

Question 17

What are the roles of bile acids and colipase in TAG digestion?

Answer 17

Bile salts are released from the gall bladder and surround the TAG. Colipase binds to the bile salts and recruits pancreatic lipase to break down the TAG into FA and 2-MG.

NOTE: Colipase is only a cofactor of pancreatic lipase, it does not have enzymatic activity, it simply works to bring the TAG and lipase in close proximity.

Question 18

What is enterohepatic circulation?

Answer 18

Bile salts work in TAG digestion, and are then resorbed in the ileum, and returned to the liver via the enterohepatic circulation

Question 19

What percentage of bile salts are recycled via enterohepatic circulation?

Answer 19

95% (5% lost in feces). So high cholesterol can be managed by disrupting the re-uptake of bile salts.

Question 20

What is the role of 2-Monoacylglycerol in lipid digestion?

Answer 20

2-MG is a product of TAG breakdown. However, after being absorbed into the intestinal epithelial cells, 2-MG and FAs must be resynthesized into TAG (requires ATP).

Question 21

What are Chylomicrons? What is their composition?

Answer 21

They are are lipoproteins that have a variable composition. They have a simple phospholipid bilayer. They are mostly TAG in interior, with a variable amount of lipid, protein, cholesterol, and cholesterol ether. They also contain Apoprotein B48 protein (intestinal form of ApoB-100, which is found in the liver).

Question 22

How do chylomicrons mature?

Answer 22

When ‘nascent’ chylomicrons reach the bloodstream, they become fully mature via an interaction (involving a transfer of proteins) with HDL (bound to ApoE and ApoCII). These mature chylomicrons (with bound ApoE and ApoCII) then interact with lipoprotein lipase on the capillary walls. (Lipoprotein lipase is activated by interaction with ApoCII). This enzyme hydrolyzes TG to form fatty acids and glycerol for uptake into tissue

Question 23

What happens to Chylomicron remnants?

Answer 23

they are are taken in by liver receptors (which were activated by ApoE) for disposal or re-use.

Question 24

Where are bile salts

a) synthesized
b) stored
c) secreted into
d) resorbed
e) recovered by?

Answer 24

a) liver
b) gallbladder
c) small intestine
d) ileum
e) enterohepatic circulation

Five percent or less of luminal bile acids are excreted in the stool under normal circumstances.

Question 25

What contributes to the differences in length between Apo100 and Apo48?

Answer 25

they both come from the same gene but Apo48 is truncated much before the Apo100 is

Question 26

Where are Apo48 and Apo100 synthesized?

Answer 26

in the ER lumen of their respective cells.

Question 27

What does insulin activate in order to facilitate breakdown of chylomicrons to FAs to be taken up by target cells?

Answer 27

Lipoprotein lipase

Question 28

How are broken down FAs from LPL remade into TAG in the target tissue for storage?

Answer 28

glucose is made into glycerol-3-p and combined with fatty acyl CoA to form TAG