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Y Biochemistry 2 > Midterm II: Lipid Transport (Ben) > Flashcards

Midterm II: Lipid Transport (Ben) Flashcards

1
Q

What is the first step of TAG digestion within the intestinal lumen?

Enzyme + products?

A

Pancreatic lipase breaks down TAG into 2 FFAs plus 2-MAG

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2
Q

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

(3 possibilities)

A
  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
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3
Q

What happens to 2-MAG which is absorbed into intestinal epithelial cells?

A

it enters the monoacylglycerol pathway in which 2 fatty acids are re-added to it before its absorption into lacteals

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4
Q

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

A

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

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5
Q

What happens to the fatty acid cleaved from 1-MAG in intestinal epithelium via intestinal lipase?

A

Acyl-CoA Synthetase activates it with CoA and it enters the phosphatidic acid pathway

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6
Q

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

A
  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
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7
Q

What happens to the TAG molecules formed in the intestinal epithelium?

What new molecule do they form + where?

Where does it go?

A

They are absorbed into lacteals to form chylomicrons for transport to the blood.

(Via lymph vessels leading to the angulus venosus)

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8
Q

What happens to some of the glycerol in intestinal epithelial cells, independent of the phosphatidic acid + MAG pathways?

A

it is absorbed directly into the hepatic portal circulation

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9
Q

What are 4 important lipoproteins?

A
  1. Chylomicrons
  2. LDL
  3. HDL
  4. VLDL
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10
Q

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)

A

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
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11
Q

What does the nascent chylomicron contain?

Which element is especially important for its assembly?

A
  • Triglycerides + Cholesterol Esters
  • Apo-B48 (required for assembly)
  • Apo-A
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12
Q

What important molecules are contributed to the nascent chylomicron to create a mature chylomicron?

What other lipoprotein contributes them them?

A
  • Apo-E
  • Apo-C

Contributed by HDL from the liver

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13
Q

Once the chylomicron is complete (via HDL apoprotein donations), what happens to it?

Be specific about an apoprotein involved in this.

A
  • 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
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14
Q

How is lipoprotein lipase activity different on some cells?

A
  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
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15
Q

What happens to a chylomicron after it releases some of its TAGs to extrahepatic tissues?

A
  • Becomes chylomicron remnant with smaller surface area + less contents
  • Remnant gives Apo-A** and **Apo-C back to HDL
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16
Q

Once the chylomicron remnant has given apoproteins back to HDL…

where does it go?

A

It is taken up by the liver via…

  • LDL receptors
  • LRP (LDL Receptor-related Protein)

…and turned back into cholesterol + bile

17
Q

What is the name of the condition of cloudy plasma involving lipid metabolism?

Why is the plasma cloudy?

What can this indicate?

A

Lipemic Plasma

  • plasma high in chylomicrons due to…
  • a recent meal
  • lipoprotein lipase deficiency
18
Q

Where does nascent VLDL come from and what is its most important apoprotein?

A
  • From fatty acids + cholesterol in the liver
  • Apo B-100 is its important structural apoprotein
19
Q

Like with chylomicrons…

What happens to nascent VLDL before it becomes mature?

And what happens after it is mature?

A
  • 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
Q

After its fatty acids have been given to extrahepatic tissues, what happens to VLDL?

A
  • Gives its Apo-C back to HDL to become…

IDL - intermediate density lipoprotein

21
Q

What are the two possible fates of IDL?

A
  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
Q

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

A

Chylomicrons + VLDL - TAG

LDL + HDL - Cholesterol + Phospholipid

23
Q

What is the general structure of a lipoprotein?

A
  • Non-Polar Core - mostly TAG and Cholesterol Esters
  • Phospholipid “Shell” - single layer of phospholipid with polar heads facing outward to aqueous medium
24
Q

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

A
  • HDL - Apo A
  • VLDL + LDL - Apo B-100
  • Chylomicrons - Apo B-48
25
Q

What are the 3 main roles of apoproteins?

And examples of each?

A
  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
Q

How + where are chylomicrons and VLDL formed?

A

Chylomicrons in intestinal epithelium and VLDL in liver

  1. Apo-B formed in RER
  2. ApoB, TAG, cholesterol, and phospholipid incorporated into particles in SER
  3. Carbohydrate residues added in Golgi apparatus
  4. Released from cells via pinocytosis
27
Q

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?

A

MTP (Microsomal Triglyceride Transfer Protein)

  • lipidates Apo B-100 with phospholipid and facilitates transfer of TAG into ER
28
Q

After VLDL2 is formed in the ER…

Where does it go for transformation to VLDL1?

How does it get there?

What happens there?

A
  • transferred to the Golgi via COP-II vesicles
  • fuses with TAG-rich lipid droplets to form VLDL1
29
Q

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

A

from phosphatidic acid, which is formed…

from phospholipids via phospholipase D which is activated by …

ARF-1 (ADP-ribosylation factor-1)

Y Biochemistry 2 (24 decks)

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