Midterm II: Lipid Transport (Ben) Flashcards Preview

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1

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

2

What happens to 2-MAG produced from breakdown of TAG via lipase in the intestine?

(3 possibilities)

  1. ~72% Directly Absorbed into intestinal epithelium
  2. ~22% Further Broken Down to glycerol + FFA via lipase
  3. ~6% Isomerized to 1-MAG via an isomerase, then absorbed

3

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

4

What happens to 1-MAG after its absorption into intestinal epithelial cells?

Intestinal lipase cleaves the last fatty acid, leaving glycerol and 1 FFA

5

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

6

What happens to the glycerol formed from 1-MAG via intestinal lipase in intestinal epithelial cells?

  1. Glycerol Kinase phosphorylates it to G-3-P
  2. 2 acyl-CoA join to make Phosphatidic Acid
  3. Phosphate is cleaved + 3rd Acly-CoA joins to make TAG

7

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)

8

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

9

What are 4 important lipoproteins?

  1. Chylomicrons
  2. LDL
  3. HDL
  4. VLDL

10

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

11

What does the nascent chylomicron contain?

Which element is especially important for its assembly?

  • Triglycerides + Cholesterol Esters
  • Apo-B48 (required for assembly)
  • Apo-A

12

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

13

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-CoAGlycerol exits the cell

 

14

How is lipoprotein lipase activity different on some cells?

 

  1. Adipose Tissue - LPL activity insulin-dependent, so fat tissue gets more fatty acids in fed state
  2. Skeletal Muscle - LPL has low Km + is activated by exercise

15

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

16

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

17

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

 

18

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

19

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

20

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

21

What are the two possible fates of IDL?

  1. Hepatic Uptake - via LDL receptor (for Apo-B/E proteins)
  2. LDL formation - loses Apo-E to become LDL
    • LDL then taken up by liver or extrahepatic tissues

22

What are the predominant lipids in each of the 4 types of lipoproteins?

Chylomicrons + VLDL - TAG

LDL + HDL - Cholesterol + Phospholipid

23

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

24

What are the major apoproteins of the four types of lipoproteins?

  • HDL - Apo A
  • VLDL + LDL - Apo B-100
  • Chylomicrons - Apo B-48

25

What are the 3 main roles of apoproteins?

And examples of each?

  1. Structure - integral, non-removable
    • ex: apo B-100 or B-48
  2. Enzyme Cofactors/Inhibitors
    • ex: Apo C-II as cofactor for liprotein lipase
    • ex: Apo A-II or C-II as inhibitor for LPL
  3. Receptor Ligands
    • ex: Apo B-100 + E for LDL receptor
    • ex: Apo E for LRP-1

26

How + where are chylomicrons and VLDL formed?

Chylomicrons in intestinal epithelium and VLDL in liver

  1. Apo-B formed in RER 
  2. ApoB, TAGcholesterol, and phospholipid incorporated into particles in SER
  3. Carbohydrate residues added in Golgi apparatus
  4. Released from cells via pinocytosis

27

After Apo B-100 is formed and enters the lumen of the ER...

what molecule facilitates the formation of VLDL2 (VLDL precursor) in the ER lumen?

MTP (Microsomal Triglyceride Transfer Protein)

- lipidates Apo B-100 with phospholipid and facilitates transfer of TAG into ER

28

After VLDL2 is formed in the ER...

Where does it go for transformation to VLDL1?

How does it get there?

What happens there?

- transferred to the Golgi via COP-II vesicles

- fuses with TAG-rich lipid droplets to form VLDL1

29

How are the TAG-rich particles added to VLDL2 in the golgi formed?

from phosphatidic acid, which is formed...

from phospholipids via phospholipase D which is activated by ...

ARF-1 (ADP-ribosylation factor-1)