Lipoproteins Flashcards
Can we use plant sterols for cholesterol synthesis?
Not really, but the consumption of plant sterols blocks update of cholesterol in the intestine
Plant sterol metabolites can be absorbed and used to make cholesterol though
Lipoprotein density from least dense to most
Major lipids in each
Chylomicron —> VLDL —> IDL —> LDL —> HDL (some HDL are denser than water)
TAGs. TAGs. CE. CE. Phospholipids
ApoA types, related lipoproteins and functions
ApoA-I on CM and HDL (helps HDL to pinch off CM with redundant PL)
- Acts in structure and LCAT activator
ApoA-II on CM and HDL (same)
- unknown function
ApoA-III on CM and HDL
- LCAT activator, satiety and other functions unknown
ApoB types, related lipoprotein and functions
ApoB-48 on CM
- transport of CM and structure
- synthesized by the intestine as a ApoB-100 that is stopped at 48% (RNA editing)
ApoB-100 on VLDL, IDL, LDL
- structure, VLDL transport and LDLreceptor ligand
- synthesized in the liver
ApoC types, lipoproteins associated with and functions
ApoC-I on CM, VLDL, IDL, LDL
- unknown function
ApoC-II on CM, VLDL, IDL, LDL
- lipoprotein lipase activator
ApoC-III on CM, VLDL, IDL, LDL
- lipoprotein lipase inhibitor
ApoE types, lipoproteins associated and functions
ApoE on CM, VLDL, IDL, LDL
- ligand for LDLreceptor and VLDL receptor
Nascent chylomicrons and mature chylomicrons contain
Nascent: Triglycerides, cholesterol/CE, ApoB-48
Mature: TAGs, CE/cholesterol, ApoA-I, ApoB-48, ApoE and ApoC-II
- ApoE and ApoC-II come from an HDL
Chylomicron remnant contains
Less cholesterol esters, cholesterol, phospholipids, and TAGs
Contains ApoB-48 and ApoE (receptor on liver)
ApoC-II and ApoA-I go to HDL
What is abetalipoproteinemia ?
Lack of apoB-48 and/or apoB-100
What is hyperlipoproteinemia?
Type I - deficiency of ApoC-II (can’t hydrolyze TAGs in lipoproteins)
Type II - deficiency ApoE (can’t absorb lipoproteins into the liver for breakdown)
Explanation of atherosclerosis
High cholesterol causes cells to block cholesterol uptake
Macrophages consume excess LDL and eventually die
Dead macrophages accumulate in injury blood vessels and create blockages
VLDL contains
Cholesterol/CE and TAGs from liver
ApoB-100, ApoC-II, ApoE
ApoC-II is transferred back to HDL to form IDL
IDL contains
ApoE, ApoB-100, decrease TAGs, high cholesterol
TAGs exchanged with HDL and CE accepted via CETP, and ApoE is lost to become LDL
What is tangier disease?
Rare autosomal disease with defective ABCA1 transporter needed for cholesterol and phospholipid uptake by nascent HDL and cells (lacking HDL as a result and increased intracellular free cholesterol)
Role of nascent HDL
Produced in liver and small intestine
Contains ApoA-I, picks up cholesterol in coating (unless Tangier disease)
LCAT esterifies cholesterol into CE
HDL delivers CE to liver, VLDL and IDL
HDL receives TAGs and PL from VLDL/IDL/LDL to return to liver
HDL trades apolipoproteins with which lipoproteins?
HDL trades ApoC-II and ApoE with chylomicrons and VLDL for activating lipoprotein lipase (ApoC-II) and binding liver receptors
Reverse cholesterol transport pathway with HDL
Unesterified cholesterol can be directly dropped off at liver by HDL
Esterified cholesterol is passed to lipoproteins by CETP which can then drop the CE off to be converted to UC
Attributes of adipocytes/lipocytes that makes weight loss difficult
Adipocytes can live up to 4 years
Once they are terminally differentiated, they are very efficient at taking up fat store
How does the cell respond to increased cholesterol concentration?
LDL binds to cell receptors in coated pits on target cell
Lysomes break down LDL into components, cholesterol is brought to the ER
1. Reduction in HMG-coA reductase expression through SREBP pathway
2. ACAT convert cholesterol to CE to be stored in vesicles in cytoplasm
3. leads to suppression of LDL receptors on the cell
4. Increased ABCA1 expression to move UC to HDL
About the LDL receptor
Very complex, multi-domain receptor
Interfaces with ApoE
SNPs in receptor polypeptides can affect receptor sensitivity to LDL
In a cell increased free cholesterol leads to:
- Decreased HMGR production via SREBP pathway
- Decreased expression of LDL receptors
- Increased ACAT (acyl-coA cholesterol acetyltransferase) converting free cholesterol –> cholesterol esters
- Increased expression of ABCA1 to move cholesterol to HDL particles (unless Tangier disease)
In a liver (parenchymal cell) free cholesterol can go which pathways?
- UC –> VLDL
- ACAT converted to CE for storage in droplets in cytoplasm
- Secreted directly into bile as free cholesterol
- Bile acids production involving Cyp7a1
Conversion of cholesterol into bile acids pathway
- Cholesterol –> 7alpha-hydroxycholesterol, by 7alpha hydroxylase
- 7alpha-hydroxycholesterol –> Chenodeoxycholic acid and cholic acid
- Addition of taurine or glycine
What is the rate limiting step of bile acid production from cholesterol?
Cholesterol –> 7alpha-hydroxycholesterol
7alpha hydroxylase/Cyp7a1
In most animals cholesterol stimulates this step, but not in humans, in humans it is stimulated by LXR bound by oxysterols
Bile acids repress this enzyme
