Absorption and Transport of Dietary Fat Flashcards
Are lipids water soluble?
No. they are hydrophobic
What defines a lipid?
It’s solubility properties, not its chemical structure
What are some examples of lipids?
1) Fatty acids
2) Solid or liquid “fats” Triacylglycerols (TAG), triglycerides (TG)
3) Membrane phospholipids (phosphatidylcholine, sphingomyelin)
4) Cholesterol
5) Steroid hormones
What is the composition of fatty acids?
they consist of a long hydrocarbon tail with a carboxylic acid head region
How many fatty acyl groups does glycerol have?
3
What are the major source of dietary fatty acids (FA)?
Triacylglycerols (TAG) a.k.a. triglycerides (TG)
What are bile salts derived from?
cholesterol
Describe the composition of bile salts
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!
What is the difference between saturated and unsaturated fatty acids?
Saturated fatty acids have NO double bonds. Unsaturated fatty acids have interspersed double bonds.
What is the function of oral and gastric lipases in relation to FAs?
function to knock off short chains of FAs from ingested TAGs
NOTE: do not effect long chain fatty acids
How does Pancreatic lipase work?
It works on TAGs and removes FAs from positions 1 and 3, releasing 2 fatty acids and a 2-Monoacylglycerol.
What does pancreatic lipase require to work?
Requires protein colipase to stabilize and localize lipase near the bile salt-TG particle
How does protein colipase work?
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
What is the role of Cholesterol esterase?
Cholesterol esterase breaks down cholesterol ester into FA and cholesterol.
What does Phospholipase A2 do?
breaks down phospholipids into FAs and lysophospholipids
Outline the steps in the digestion of TAG to the formation of chylomicrons
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.
What are the roles of bile acids and colipase in TAG digestion?
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.
What is enterohepatic circulation?
Bile salts work in TAG digestion, and are then resorbed in the ileum, and returned to the liver via the enterohepatic circulation
What percentage of bile salts are recycled via enterohepatic circulation?
95% (5% lost in feces). So high cholesterol can be managed by disrupting the re-uptake of bile salts.
What is the role of 2-Monoacylglycerol in lipid digestion?
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).
What are Chylomicrons? What is their composition?
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).
How do chylomicrons mature?
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
What happens to Chylomicron remnants?
they are are taken in by liver receptors (which were activated by ApoE) for disposal or re-use.
Where are bile salts
a) synthesized
b) stored
c) secreted into
d) resorbed
e) recovered by?
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.