Plasma Lipoproteins Flashcards
What is the normal lipid profile? (mg / 100ml)
Total lipid: 400-800 Triglycerides: 40-300 Total cholesterol: 90-200 Phospholipids: 150-380 Free fatty acids: 8-14
Four modes of lipid transport in the blood?
- Fatty acids from adipose tissue via albumin
- Dietary lipid from intestine to other tissues (chylomicrons)
- Endogenously synthesized lipids from liver to other tissues (VLDLs)
- Reverse transport of cholestrer and esters from periphery to liver (HDL)
Four major classes of lipoprotein particles?
Chylomicrons (contains most TGs; A, C, E, B-48)
VLDL (B-100, C, E)
LDL (B-100)
HDL (A, C, E)
% of lipids and proteins of the classes of LP particles?
Chylomicrons: 99% lipid, 1% protein
VLDL: 92 to 8
LDL: 80 to 20
HDL: 50 to 50
Apo AI
Activates LCAT, an enzyme that converts free cholesterol into cholesteryl ester, which is then sequestered into the core of a lipoprotein particle, eventually making the newly synthesized HDL
Apo B-100
Involved in VLDL assembly and secretion
Apo CII
Activator of LPL
Apo CIII
Inhibitor of LPL
Apo E
Acts as “reuptake;” Is a ligand for binding several lipoproteins to the LDL receptor; “recognition”
Chylomicron characteristics
- Is the least dense of lipoproteins
- Contains the most TAGs
- Has Apo B-48, Apo E and Apo CII
VLDL characteristics
- Contains TAG and cholesteryl esters in high concentrations
- Has Apo B-100, Apo CI, Apo CIII and Apo E
IDL characteristics
- Results from significant amount of TAGs removed from VLDL
- Contains Apo B-100, Apo CI, Apo CII, Apo CIII and Apo E
LDL characteristics
- Produced by removal of TAGs from VLDL
- Is enriched in cholesterol / cholesteryl esters
- Apo B-100 is major protein
HDL characteristics
- Produced from enzymatic conversion of LDL and VLDL cholesterol to cholesteryl esters
PCSK9
- Is a protease that degrades the LDL receptor after uptake of receptor-LDL complex
- Reduces [LDL receptors] in the blood
Action of LPL
Digests TGs of chylomicrons to fatty acids (FAs) and glycerol
Synthesis, processing and secretion of VLDL
Proteins synthesized on RER are packaged with TAGs in the ER and Golgi, to form VLDL. They are then transported to cell membrane and secreted by exocytosis
Elevations in plasma TG are usually a result of…
…increased VLDL levels!
Perilipins surround…
…the TGs that are stored within cardiomyocytes in lipid droplets
Perilipins role?
Modulate the actions of ATGL, which removes the first fatty acid from triglyceride
After ATGL removes the FFA, the second and then final FAs are removed by…
…HSL and then MGL. These FAs then complex with CoA via ACSL
In a pro-inflammatory state, enlarged adipocytes produce…
…monocyte chemotaxis protein (MCP-1), attracting macrophages to the tissue
What do macrophages, attracted to adipocytes, do?
They produce TNF alpha, favoring the export of FAs to muscle.
What does ectopic lipid do, regarding GLUT 4?
Interferes with GLUT 4 movement to the myocyte surface, producing INSULIN RESISTANCE
Action of fibrates on the liver
Fibrates activate PPAR-alpha in the liver, leading to:
- Increased beta oxidation of FAs, thus decreasing the liver’s secretion of VLDLs
- Increased clearance of chylomicron remnants
- Increased levels of HDLs
- Increased LPL activity, promoting rapid VLDL turnover
TZD (Thiazolidinedione) drug effects?
TZDs stimulate PPAR-gamma, promoting fat cell differentiation and decreasing blood glucose.
- Promotes glucose uptake into adipose tissue (increases expression of GLUT 4)
- Upregulates PEPCK, allowing FFA to be loaded into TAGs
Free cholesterol affects what 3 proteins?
- Induces ACAT (increase intracellular storage)
- Represses HMG-CoA (decreased cholesterol biosyn)
- Reduces synthesis / speeds up degradation of LDL receptors
Role of ABCA1 (carrier of cholesterol)
ABCA1 and ApoA-I (nascent HDL) combine. If ABCA1 is defective, HDLs cannot form (Tangier dx)
Cellular responses to excess plasma membrane cholesterol
- Downregulates the LDL receptor to stop importing in more cholesterol
- Transports excess cholesterol to the plasma membrane, exporting it out to HDL particles via ATP binding cassettes
- Lowers activity of HMG-CoA reductase
Role of LCAT?
Takes cholesterol from the outer leaflets of the cell and esterifies it. HDL then trades the newly esterified cholesterol for a TG from VLDL via CETP
Increasing TG will (increase/decrease) [HDL]
Decrease!
How do HDLs protect against cardiovascular disease?
- Promotes efflux of cholesterol from macrophages
- Inhibits the oxidative modification of LDLs
- Inhibits vascular inflammation and inhibits thrombosis
Role of SR-BI (Scavenger receptor B I)?
Uptakes HDL into the tissue
CETP (CE and TG transfer) transforms _____ back to _____
HDL2 is transformed back to HDL3
Exercise decreases catabolism of HDL and thus, increases HDL levels. How?
- CETP activity is decreased
- Conversion of HDL3 to HDL2 is decreased
- Levels of LPL are increased (chylomicrons can be disassembled better and less TAGs come to the liver
