Lipoproteins Flashcards
1
Q
Chylomicrons
A
- released by intestinal mucosal cells (into lymph: thoracic duct–>L brachiocephalic vein)
- TAGs resynthesized from 2-MAGs
- ApoB48 (RNA editing, C-deaminase)
- Cholestoryl Esters
- Lipid soluble vitamins
- Remnants (after TAGs removed) absorbed by liver
- dietary lipids
- float on top of blood sample, not present in fasting blood
- 90% TAGs, 2% protein, 3% phospholipid, 5% cholesterol and CE (highester % of TAGs in lipoproteins, major source of TAGs in blood with VLDLs)
- ApoCII (recieved from HDLs, also tranfered back)-activates LPL
- ApoE (recieved from HDLs)-necessary for CM remnant uptake by liver
2
Q
VLDLs
A
- formed and released by liver with products of de novo fatty acid and cholesterol synthesis following carbohydrate rich meal
- for storage or use
- 60% TAG, 20% cholesterol and CE, 15% phospholipids, 5% protein (major source of TAGs in blood with chylomicrons)
- ApoB100 for release into blood
- ApoCII (recieved from HDLs, also transfered back)-activates LPL
- ApoE (recieved from HDLs)-necessary for IDL uptake by liver
- also called pre-β lipoproteins
3
Q
LDLs
A
- VLDLs after TAGs are removed by lipoprotein lipase (via IDLs)
- 50% Cholestrol and CE, 22% phospholipids, 8% TAGs, 20% protein (highest % of Cholesterol and CE)
- Normal serum LDL <200 mg/dL (or 180), LDL-C is 100-130 mg/dL, increase with age
- have ApoB100
- 70% taken up by liver, 30% to extrahepatic tissues
- t1/2=4 days
- LDL-B is most dense and small (more easily penetrate endothelium, risk factor for CHD)
- LDL-A is less dense
- also called β-lipoproteins
4
Q
HDLs
A
- transport cholesterols from tissues to liver (reverse cholesterol transport)
- 40% protein, 30% phospholipid, 25% Cholesterol and CE, 5% TAGs (HDL-2 specifically, highest in protein)
- Resevoir of Apolipoproteins (ApoA1* (70%, for reverse cholesterol transport), ApoCII+ApoE 30%)
- Normal levels b/w 50-70 mg/dL
- higher in females than males, increases with exercise
- risk factor: males: 3 > 2 >1 (size is opposite)
- also called α-lipoproteins
- Potential anti-atherogenic properties
- CEs formed by LCAT activated by ApoA-1, also need free cholesterol ABC-transporter and CETB (reverse cholesterol transport)
- Paraoxonase and PAF acetylhydrolase-reduce LDL oxidation
- Plaque stabilization properties (reduce plaque lipid content, reduce macrophage content, increase plaque smooth muscle content and prevent rupture)
- HDL2 delivers cholesteryl esters to liver or steriodogenic tissue via SR-B1
5
Q
Normal Fasting blood TAG level
A
100-150 mg/dL
6
Q
Lipoprotein Lipase
A
- cleaves TAGs in lipoproteins to 2 FA and MAG (last fatty acid is eventually cleaved as well, free glycerol taken up by hepatocytes, Fatty acids used for β-oxidation or storage as TAGs)
- anchored in place in capillaries (by heparan sulfate) mostly in heart and adipose (and skeletal muscle)
- Activated by ApoCII (in VLDLs and CMs high % of TAGs, recieved from HDLs)
- synthesized mainly by heart and adipose, N-glycosylated, bound to luninal surfatce of vascular endothelium
- (active as dimer)
- heart isozyme has low Km
- fat isozyme is activated by insulin (high blood glucose), also high Km (faster)
7
Q
CM remnants
A
- still contain dietary lipids, lipid soluble vitamins, CEs
- taken up by liver as source of cholesterol
- ApoE, ApoB48
8
Q
ApoB48
A
- found in CMs, needed for release from mucosal cells
- Also for receptor recognition of CM remnants
9
Q
ApoB100
A
- Found in VLDLs for relase into blood
- If oxidized LDLs cannot be taken up normally and are phagocytized by macrophages–>foam cells
- Required for LDL-receptor
10
Q
ApoCII
A
- activates LPL
- found in VLDLs and CMs (high % of TAGs, received from HDLs)
- Given back to HDLs as well
11
Q
ApoE
A
- found on (HDLs), VLDLs, CMs, IDLs, CM remnants, LDLs
- Donated to VLDLs by HDLs
- used for uptake of IDLs and CM remnants by liver
- In general needed for remnant receptors
- Used by LRP for recognition of IDLs
- Different alleles: ApoE-3 most common (75%), ApoE-2 (10%) has poor binding to remnant receptor
12
Q
IDLs
A
- should have ApoB100, ApoCII (this is when they start loosing it, probably very little still have it), ApoE (used for uptake by liver)
- 50% taken up by liver
- 50% further broken down to LDLs
13
Q
HTGL
A
- Hepatic Lipase (acting on TAGs) (also has phospholipase activity)
- Cleaves TAGs in IDLs, similiar to LDL
- Bound via Heparan sulfate in hepatic capillaires
14
Q
LDL receptors
A
- expressed in many (all?–>all cells need cholesterol for membranes) tissues including liver and macrophages
- used for uptake of LDLs (and IDLs in liver)
- recognizes ApoB100
- Down-regulated in liver following cholesterol rich meal: high CM remnants (high cholesterol)–|LDL receptor–>increased serum LDL
- down regulated in extrahepatic tissues when cells have sufficient cholesterol
- do not regonized oxLDLs
- LDL-receptor-related protein (LRP) (said something about taking up IDLs in liver)
- can be recycled, also use catherin to form endosomes (endocytosis)
15
Q
Some oxidizing agents and antioxidents
A
oxidants: O2-⋅, NO⋅, H2O2
antioxidents: Vit E, Vit C (ascorbic acid), β-carotene
16
Q
SR-A
A
- low affinity (high Km), nonspecific, nonregulated scavenger receptor on macrophages
- macrophages use to phagocitize oxidized LDLs (oxLDL) (I guess it’s able to bind to the oxidized ApoB100 or something)
- macrophage has generally downregulated its LDL receptor when this is being used
17
Q
Foam cell
A
- a macrophage (or smooth muscle cell) that has consumed too many oxLDLs
- is large, has irregular membrane, and many lipid droplets
- releases growth factors and cytokines that stimulate migration of smooth muscle (move from media to intima, proliferate, produce collagen, and take up lipid potentially becoming foam cells as well) (fibrofatty atheroma–>atherosclerosis–>potentially MI or stroke or CHD etc)
18
Q
Lipoprotein(a)
A
- Lp(a)
- Similar to LDL but has unusual structure (“kringles”
- # ’s increased by trans-FAs
- # ’s lowered by ω-3s and niacin
- Risk factor for CHD
