Midterm II: Lipid Transport (Ben) Flashcards
What is the first step of TAG digestion within the intestinal lumen?
Enzyme + products?
Pancreatic lipase breaks down TAG into 2 FFAs plus 2-MAG
What happens to 2-MAG produced from breakdown of TAG via lipase in the intestine?
(3 possibilities)
- ~72% Directly Absorbed into intestinal epithelium
- ~22% Further Broken Down to glycerol + FFA via lipase
- ~6% Isomerized to 1-MAG via an isomerase, then absorbed
What happens to 2-MAG which is absorbed into intestinal epithelial cells?
it enters the monoacylglycerol pathway in which 2 fatty acids are re-added to it before its absorption into lacteals
What happens to 1-MAG after its absorption into intestinal epithelial cells?
Intestinal lipase cleaves the last fatty acid, leaving glycerol and 1 FFA
What happens to the fatty acid cleaved from 1-MAG in intestinal epithelium via intestinal lipase?
Acyl-CoA Synthetase activates it with CoA and it enters the phosphatidic acid pathway
What happens to the glycerol formed from 1-MAG via intestinal lipase in intestinal epithelial cells?
- Glycerol Kinase phosphorylates it to G-3-P
- 2 acyl-CoA join to make Phosphatidic Acid
- Phosphate is cleaved + 3rd Acly-CoA joins to make TAG
What happens to the TAG molecules formed in the intestinal epithelium?
What new molecule do they form + where?
Where does it go?
They are absorbed into lacteals to form chylomicrons for transport to the blood.
(Via lymph vessels leading to the angulus venosus)
What happens to some of the glycerol in intestinal epithelial cells, independent of the phosphatidic acid + MAG pathways?
it is absorbed directly into the hepatic portal circulation
What are 4 important lipoproteins?
- Chylomicrons
- LDL
- HDL
- VLDL
What are the general protein to triglyceride ratios of the important lipoproteins?
(not specific numbers, just generally which ones are higher protein, which are higher TAG)
Basically, the less dense (ie LDL) the lower the protein content + higher TAG content
In order from lowest protein:TAG ratio to highest:
- Chylomicron
- VLDL
- LDL
- HDL
What does the nascent chylomicron contain?
Which element is especially important for its assembly?
- Triglycerides + Cholesterol Esters
- Apo-B48 (required for assembly)
- Apo-A
What important molecules are contributed to the nascent chylomicron to create a mature chylomicron?
What other lipoprotein contributes them them?
- Apo-E
- Apo-C
Contributed by HDL from the liver
Once the chylomicron is complete (via HDL apoprotein donations), what happens to it?
Be specific about an apoprotein involved in this.
- Apoprotein-C2 activates lipoprotein lipase on capillary surface in extrahepatic tissues
-
Fatty acids from chylomicron enter extrahepatic cells (due to conc. gradient)
- Intracellular FAs are converted to Acyl-CoA + Glycerol exits the cell
How is lipoprotein lipase activity different on some cells?
- Adipose Tissue - LPL activity insulin-dependent, so fat tissue gets more fatty acids in fed state
- Skeletal Muscle - LPL has low Km + is activated by exercise
What happens to a chylomicron after it releases some of its TAGs to extrahepatic tissues?
- Becomes chylomicron remnant with smaller surface area + less contents
- Remnant gives Apo-A** and **Apo-C back to HDL
Once the chylomicron remnant has given apoproteins back to HDL…
where does it go?
It is taken up by the liver via…
- LDL receptors
- LRP (LDL Receptor-related Protein)
…and turned back into cholesterol + bile
What is the name of the condition of cloudy plasma involving lipid metabolism?
Why is the plasma cloudy?
What can this indicate?
Lipemic Plasma
- plasma high in chylomicrons due to…
- a recent meal
- lipoprotein lipase deficiency
Where does nascent VLDL come from and what is its most important apoprotein?
- From fatty acids + cholesterol in the liver
- Apo B-100 is its important structural apoprotein
Like with chylomicrons…
What happens to nascent VLDL before it becomes mature?
And what happens after it is mature?
- HDL gives it both Apo C + Apo E
- mature VLDL is acted on by LPL (activated by Apo C2)
- VLDL gives its FAs to extrahepatic tissues + glycerol exits cell
After its fatty acids have been given to extrahepatic tissues, what happens to VLDL?
- Gives its Apo-C back to HDL to become…
IDL - intermediate density lipoprotein
What are the two possible fates of IDL?
- Hepatic Uptake - via LDL receptor (for Apo-B/E proteins)
-
LDL formation - loses Apo-E to become LDL
- LDL then taken up by liver or extrahepatic tissues
What are the predominant lipids in each of the 4 types of lipoproteins?
Chylomicrons + VLDL - TAG
LDL + HDL - Cholesterol + Phospholipid
What is the general structure of a lipoprotein?
- Non-Polar Core - mostly TAG and Cholesterol Esters
- Phospholipid “Shell” - single layer of phospholipid with polar heads facing outward to aqueous medium
What are the major apoproteins of the four types of lipoproteins?
- HDL - Apo A
- VLDL + LDL - Apo B-100
- Chylomicrons - Apo B-48
