Lipoprotein Metabolism Flashcards

1
Q

What is the composition of lipoproteins?

A

Hydrophobic core (CE, TAGs, fat-soluble vitamins) surrounded by amphipathic lipids (phospholipids, free cholesterol) and apolipoproteins

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2
Q

What are the three structural proteins and which lipoproteins are made of each?

A
  • Apo B-48: CM, CM remnants
  • Apo B-100: VLDL, IDL, LDL
  • Apo A-I: HDL
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3
Q

What do CMs transport?

What do VLDLs transport?

A
  • CMs transport dietary lipids

- VLDLs transport liver-synthesized TAGs

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4
Q

Besides being a structural protein, what is the other function of Apo A-I?

A

Activates LCAT

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5
Q

Besides being a structural protein, what is the other function of Apo B-100?

A

LDL-receptor ligand

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6
Q

Which three lipoproteins use Apo C-II? What is the function of Apo C-II?

A

Apo C-II is found in CM, VLDL and HDL

Apo C-II activates LPL

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7
Q

Which five lipoproteins use Apo E?

A
  • CM
  • CM remnants
  • VLDL
  • IDL
  • HDL
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8
Q

Order the five lipoproteins by size.

A

CM > VLDL > IDL > LDL > HDL

inversely related to density

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9
Q

Order the five lipoproteins by density.

A

HDL > LDL > IDL > VLDL > CM

inversely related to size

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10
Q

What is the purpose of CM metabolism?

A

Transport dietary fat to peripheral tissues

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11
Q

What are the six steps of CM metabolism?

A
  1. CMs are synthesized from dietary lipids and Apo B-48 in the small intestine - MTP is needed to load the CM with lipids
  2. CM is released from the small intestine to the lymphatic system then the bloodstream
  3. In the blood, CMs become mature when Apo C-II and Apo E are added from circulating HDL
  4. At tissue cells, LPL (activated by Apo C-II) degrades TAGs - glycerol travels to liver and FAs used/stored
  5. Apo C-II returned back to HDLs, leaving behind the CM remnant which contains Apo B-48, Apo E, lots of C/CE, and few TAGs
  6. CM remnants bind to hepatic Apo E receptors on the liver and are taken up by endocytosis, where free cholesterol, AAs and fat-soluble vitamins are released
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12
Q

Where is LPL found in the body?

Which two tissue cell types are LPLs specifically expressed, and what stimulates expression of the LPL?

A

Attached to the extracellular matrix of epithelial cells in capillaries (not in blood circulation)

  • Adipose: stimulated by high I/G ratio (insulin) - used for fat storage in fed state
  • Muscle: stimulated by low I/G ratio (epi/glucagon) - used for energy in fasting state
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13
Q

What is the source of Apo proteins in the cell?

A

HDLs circulating in the blood

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14
Q

What is the purpose of VLDL/IDL/LDL metabolism?

A

Transport liver-synthesized TAGs (fed) or liver-repackaged TAGs (fasting) to peripheral tissues

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15
Q

What are the seven steps of VLDL/IDL/LDL metabolism?

A
  1. TAG-rich VLDLs are assembled with Apo B-100 in the liver - MTP is needed to load the VLDLs with lipids
  2. VLDLs are released from the liver into the lymphatic system then the bloodstream
  3. In the blood, VLDLs become mature when Apo C-II and Apo E are added from circulating HDL
  4. At tissue cells, LPL (activated by Apo C-II) degrades TAGs - glycerol travels to liver and FAs used/stored
  5. Apo C-II returned back to HDLs, leaving behind the IDL Apo B-100, Apo E, lots of C/CE, and few TAGs
  6. IDLs are either taken up by the liver OR digested by Hepatic Lipase, turning into LDLs
  7. LDLs either bind to LDL receptors on the surface of the liver OR bind to LDL receptors on the surface of non-liver tissues - taken up by endocytosis, where free cholesterol, AAs and fat-soluble vitamins are released
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16
Q

What are the two fates of IDLs?

A
  • Taken up via Apo E receptors on the liver

- Further digested by Hepatic Lipase to lower TAGs and donate their Apo E to HDLs, turning themselves into LDLs

17
Q

What are the two fates of LDLs?

A
  • Bind to LDL receptors on the surface of liver (70%)

- Bind to LDL receptors on the surface of non-liver tissues (30%)

18
Q

Which type of structural proteins do LDL receptors only recognize?

A

Apo B-100 (found in LDLs)

19
Q

How does atherosclerosis relate to VLDL/IDL/LDL metabolism?

A

When there are excess LDLs present in the blood and the LDL receptors are all saturated, the LDLs are available to macrophages - macrophages fill with oxidized LDL and accumulate, while the body tries to wall off the LDL-stuffed macrophages with new tissue (plaque) causing atherosclerosis

20
Q

Which of the lipoproteins are cleared from the blood circulation via Apo E-receptor-mediated endocytosis?

A

CM remnants and IDLs

21
Q

What are the eight steps of HDL metabolism?

A
  1. HDLs are synthesized with Apo A-I, Apo C-II and Apo E in the liver and small intestine
  2. Nascent HDLs are released into the lymphatic system then the bloodstream
  3. HDLs derive cholesterol from cholesterol-loaded cells in the blood in order to return it to the liver for elimination (reverse cholesterol transport) - as they fill with C, they become more globular and take on their mature form
  4. Cholesterol is trapped in HDL when it is converted from cholesterol to CE by the LCAT enzyme
  5. CEs accumulate in HDL causing it to transition from a CE-poor HDL (HDL3) to a CE-righ HDL (HDL2)
  6. The protein, CTEP, transfers some of the CE from HDL to VLDL in exchange for TAGs
  7. The liver uptakes cholesterol and CEs via the SR-B1 receptor that binds to HDL - when depleted of cholesterol and CE, HDL dissociates from the SR-B1 receptor and re-enters the bloodstream
  8. Old HDL receptors are eventually taken out of the bloodstream by Apo E receptors
22
Q

What is reverse cholesterol transport and which metabolism process is it found in?

A

Reverse cholesterol transport occurs in HDL metabolism
- It involves the ability for HDL to remove cholesterol from cholesterol-loaded cells in order to transport the cholesterol to the liver for elimination

23
Q

What is the name of the protein utilized in reverse cholesterol transport? What is this protein’s function?

A

ABCA1 protein is used to move cholesterol from the inner leaflet of the cell to the outer leaflet membrane where HDL can accept it

24
Q

What is an alternative name for the LCAT enzyme? Which Apo protein is it activated by?

What step of HDL metabolism allows for inhibition of LCAT to be relieved?

A

LCAT enzyme = PCAT enzyme
LCAT is activated by Apo A-I

When CE is transferred from HDLs to VLDLs in exchange for TAGs, inhibition of LCAT is lifted and more cholesterol can be converted to CEs for further exchanging

25
Q

The actions of which two structures in HDL metabolism produce a TAG-rich HDL particle?

A
  • CETP: exchanges CE for TAG

- SR-B1 receptors: allows the liver to uptake cholesterol and CEs to make room for more TAG

26
Q

What enzyme are TAG-rich HDL particles acted on by? What does this produce/recycle?

A

Hepatic Lipase degrades the TAGs in HDL, which produce HDL3s that can be recycled back into the blood to become HDL2s

27
Q

What is the fate of the CE transferred from HDLs to VLDLs?

A

CE in VLDLs are ultimately taken up by the liver when VLDLs are catabolized to IDLs then LDLs