Lipoprotein complexes and cholesterol transport Flashcards
In the liver, ___ and ___ are repackaged into very low density lipoprotein complexes (VLDLs). What can happen to VLDL from there?
TGs and cholesterol are repackaged into VLDLs, which are secreted into the blood.
Lipoprotein lipase may deplete teh TGs and the VLDL remnants are returned to the liver
OR
Converted into LDLs, which go back to the liver OR supply cholesterol to the extrahepatic tissues.
Lipoprotein complexes
Different percentages of phospholipid + cholesterol + TGs
Apolipoprotein on the outer surface
Most of the apolipoproteins are synthesized in the liver. Which two are synthesized in the intestine?
ApoA-1 - Intestine AND liver
ApoB-48- Intestine
Which apolipoproteins are the only ones that isn’t used by chylomicrons?
ApoA-1
&
ApoB-100
ApoA-1: Tissue source, lipoprotein distribution, function
ApoB-48: Tissue source, lipoprotein distribution, function
Intestine
Chylomicrons
Assembly & secretion of chylomicrons from intestinal mucosa
ApoB-100: Tissue source, lipoprotein distribution, function
Liver
VLDL, IDL, LDL
- VLDL assembly & secretion
- Structural component of VLDL, IDL, LDL
- Ligand for LDL receptor
ApoC-II: Tissue source, lipoprotein distribution, function
Liver
Chylomicrons, VLDL, IDL, HDL
Activates lipoprotein lipase (LPL)
ApoE: Tissue source, lipoprotein distribution, function
Liver
Chylomicron remnants, VLDL, IDL, HDL
- Ligand for binding several lipoprotiens to the LDL receptor, the LDLreceptor-related protein, and to a separate ApoE receptor
Path of chylomicrons
How does it provide fFAs to extrahepatic tissues and then cholesterol to the liver?
- Synthesis w/Apo-B-48 in the intestine to transport lipids
- Enter lymphatic system then blood, where it takes ApoC-II & ApoE from HDL
- ApoCII activates lipoprotein lipase –> TGs are hydrolyzed to fFAs that go to muscle, adipose, or other extrahepatic tissues and glycerol that goes to the liver for glyceroneogenesis or gluconeogenesis.
- Different LPLs have different Kms!
- CM remnants (depleted of TGs) are now mostly cholesterol and give their ApoC-II back to HDLs, then head to the liver using ApoE as a ligand.
ApoC-II on the chylomicron activates LPLs to hydrolyze TGs in muscle, adipose, and other extrahepatic tissues.
LPLs in different tissues have different Kms.
Which LPL has the higher Km - adipose or muscle?
Adipose LPL has the higher Km, so it digests TGs only when [chylomicrons] are high.
Muscle LPLs have the lower Km to allow continual access to FAs even at lower [chylomicron].
Which has more TG content- chylomicrons or VLDLs?
Chylomicrons have more TGs
Fate of VLDL and LDLs
- Liver synthesizes VLDLs from TGs (mostly) + cholesterol + ApoB-100 (required for synthesis & secretion)
- Get an ApoC-II and ApoE from HDLs in the blood
- ApoC-II activates an LPL, providing fFAs for extrahepatic tissues & losing TG content –> IDL –> LDL
- ApoCII and ApoE are returned to the HDL
- The remaining ApoB-100 is the major ligand for LDL receptor-mediated endocytosis so the LDL can deliver cholesterol and its minor remaining TGs to peripheral tissues.
LDL uses its ApoB-100 to cause receptor-mediated endocytosis - In the endosome, the LDL receptor is recycled back to the surface while the LDL complex is broken down in the lysosome –> everything is used, including cholesterol.
What happens if you have excessive cholesterol? Deficient cholesterol?
Excessive cholesterol:
- Inhibits HMG-CoA reductase to stop making cholesterol
- Inhibits synthesis of new LDL receptors to stop bringing it in
- Activate ACAT, which esterifies the excess cholesterol to FAs
Deficient cholesterol reverses all of these.
why is LDL is the “bad” cholesterol involved in atherosclerosis and coronary heart disease?
- When it oxidizes into oxLDL, it damages artery walls
- Monocytes adhere and become macrophages that engulf the oxLDL through upregulated scavenger receptors –> becomes a foam cell
- Foam cells accumulate and release growth factors & cytokines that stimulate migration of smooth muscle to enter the intima and secrete collagen –> atherosclerotic plaque
- Plaque can grow and rupture into the artery as a thrombus that grows until it occludes the artery