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BIOC 311 > M3: Lipoproteins L21 > Flashcards

M3: Lipoproteins L21 Flashcards

1
Q

What is the general structure of a lipoprotein?

A

Polar surface (amphipathic molecules):
-Apolipoproteins
-Free cholesterol (ampiphilic non-esterified cholesterol)
-Phospholipids
Neutral lipid core:
-Cholesteryl ester (neutral esterified hydrophobi cholesterols)
-Triacylglycerides

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2
Q

What are lipoproteins? Name them.

A

Circulating lipid carriers composed of a neutral lipid core, a monolayer of polar surface lipids and at least one apolipoprotein.

  • Chylomicrons
  • Very-low density lipoprotein (VLDL)
  • Intermediate density lipoprotein (IDL)
  • Low density lipoprotein (LDL)
  • High density lipoprotein (HDL)
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3
Q

What are apolipoproteins?

A

amphipatic proteins that insert in lipoproteins and serve as ligand for lipoprotein recognition and docking

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4
Q

Put lipoproteins in order from lowest to highest density.

A 
Chylomicrons
VLDL
IDL
LDL
HDL
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5
Q 
What is the:
1. Coat composition
2. Core composition
3. Place of origin
4. Target tissue
5. Main function
of Dietary micelles?
A
  1. Coat composition: Bile salts
  2. Core composition: CE & TAG
  3. Place of origin: Stomach
  4. Target tissue: Intestine
  5. Main function: Solubiize dietary fats in GIT.
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6
Q 
What is the:
1. Coat composition
2. Core composition
3. Place of origin
4. Target tissue
5. Main function
of chylomicrons?
A
  1. Coat composition: Cholesterol, PL, ApoB-48, ApoC, ApoE
  2. Core composition: TAG, CE
  3. Place of origin: Intestine
  4. Target tissue: Muscle & adipose
  5. Main function: Transports dietary cholesterol and TAG to the muscle and adipose.
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7
Q 
What is the:
1. Coat composition
2. Core composition
3. Place of origin
4. Target tissue
5. Main function
of VLDL?
A
  1. Coat composition: Cholesterol, PL, ApoB-100, ApoC, ApoE
  2. Core composition: TAG, CE
  3. Place of origin: Liver
  4. Target tissue: Muscle & adipose
  5. Main function: dietary and endogenous cholesterol and TAG transported to muscle and adipose.
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8
Q 
What is the:
1. Coat composition
2. Core composition
3. Place of origin
4. Target tissue
5. Main function
of LDL?
A
  1. Coat composition: ApoB-100, Cholesterol, PL
  2. Core composition: CE
  3. Place of origin: IDL (VLDL remnant)
  4. Target tissue: Peripheral cells & liver
  5. Main function: Carries leftover cholesterol from IDL to peripheral tissues and liver.
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9
Q 
What is the:
1. Coat composition
2. Core composition
3. Place of origin
4. Target tissue
5. Main function
of HDL?
A
  1. Coat composition: ApoA-1, Cholesterol, PL
  2. Core composition: CE & some TG
  3. Place of origin: Peripheral tissues
  4. Target tissue: Liver
  5. Main function: Returns excess cholesterol from peripheral tissues to the liver.
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10
Q

What is the main function, coat, and core composition of chylomicron remnants?

A

Main function: Carry leftover dietary cholesterol (and CE) and TAG to the liver.
Coat: ApoB-48, ApoE
Core: CE (major), TAG (depleted)

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11
Q

Describe the cycle of a chylomicron.

A
  1. Dietary lipids are ingested and solubilized in the stomach by bile salts and travel to the small intestine.
  2. Lipids are taken up by enterocytes and chylomicrons are secreted into the blood.
  3. In the capillaries, when they encounter LPL (lipoprotien lipase) on the surface of muscle and adipose tissue, the ApoC binds to LPL.
  4. LPL digests the TAG to form free FA and they are taken up by the tissues.
  5. Chylomicron remnants are formed which give their components to the liver via LRP and LDLR. LRP binds ApoB48 and LDLR binds ApoE.
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12
Q

Describe the cycle of a chylomicron.

A
  1. Dietary lipids are ingested and solubilized in the stomach by bile salts and travel to the small intestine.
  2. Lipids are taken up by enterocytes and chylomicrons are secreted into the blood.
  3. In the capillaries, when they encounter LPL (lipoprotien lipase) on the surface of muscle and adipose tissue, the ApoC binds to LPL.
  4. LPL digests the TAG to form free FA and MAG and they are taken up by the tissues (some CE is taken up too).
  5. Chylomicron remnants are formed which give their components to the liver via LRP and LDLR. LRP binds ApoB48 and LDLR binds ApoE.
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13
Q

Explain lipoprotein metabolism starting from VLDL and ending with LDL.

A
  1. The liver excretes VLDL into the blood.
  2. When they reach LPL on the surface of adipose and muscle, ApoC binds.
  3. LPL digests the TAG to form free FA and MAG and they are taken up by the tissues (some CE is taken up too).
  4. IDL is formed.
  5. IDL goes back to the liver via LDLR binding with ApoE.
  6. HL (hepatic lipase) is an enzyme that lipolyses the remaining TAG’s and takes them up.
  7. LDL is formed.
  8. LDL either go to the liver via LDLR binding with ApoB-100, or they go to peripheral tissues via LDLR biding with ApoB-100.
  9. At the peripheral tissues and liver, the LDL delivers CE for membrane synthesis and hormone synthesis.
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14
Q

Describe the cholesterol uptake from an LDL via LDLR.

A
  1. LDL particle coated with ApoB100 binds to ApoB receptor (LDL receptor) at surface of cell.
  2. Clathrin coat assembles and generates a clathrin coated pit that is invaginated. Clathrin coated vesicle is released in the cell and clathrin dissociates and returns to the surface, but the LDL cargo gets into the endosomal pathway.
  3. In the endosomal pathway there’s a change in pH (acidification), which disrupts the interactions between ApoB and the receptor (LDLR).
  4. The free receptor now returns to the surface in a vesicle for a second round of taking up LDL.
  5. The leftover vesicle goes to the lysosome and is digested where all the cholesteryl esters that were in the LDLs are metabolized. So the cells are going to re-esterify the cholesterol under the form of cholesteryl esters in lipid droplets.
  6. The pool of leftover free cholesterol (not esterified) can be mixed with the pool of free cholesterol that is found at the surface of the ER and can serve as a regulatory mechanism of the de-novo cholesterol synthesis in the cell.
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15
Q

Describe reverse cholesterol transport.

A

Reverse cholesterol transport is the formation of HDL in peripheral tissues (or macrophages) that is then brought to the liver.

  1. Surface cholesterol (free cholesterol) and phospholipids are acquired by the lipid poor ApoA-1 to generate Nascent HDL (pre-HDL) particles. This is done through a transporter called ABCA1.
  2. Esterification (in plasma) of cholesterol on surface of Pre-HDL by LCAT enzyme. Generates Cholesteryl esters which go to the core. The cholesterols that don’t get esterified remain on the surface.
  3. Further esterification via LCAT so particles get bigger. (almost fully mature)
  4. Happening in plasma: Exchange of triglycerides from VLDL for CE from HDL. So TG go into the HDL particles and mature them and CE go to VLDL. Done through CETP enzyme. (Fully mature)
  5. Mature HDL docks on the surface of the liver through SRB1 receptor which interacts with ApoA-1. Fully enriched in Cholesteryl esters and triglycerides. Delivers to the liver.
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16
Q

What does the liver do with the excess cholesterol that is returned to it?

A

It is used for the synthesis of bile salts.

BIOC 311 (31 decks)

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