Plasma Lipoproteins

Question 1

What is the normal lipid profile? (mg / 100ml)

Answer 1

Total lipid: 400-800
Triglycerides: 40-300
Total cholesterol: 90-200
Phospholipids: 150-380
Free fatty acids: 8-14

Question 2

Four modes of lipid transport in the blood?

Answer 2

• 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)

Question 3

Four major classes of lipoprotein particles?

Answer 3

Chylomicrons (contains most TGs; A, C, E, B-48)
VLDL (B-100, C, E)
LDL (B-100)
HDL (A, C, E)

Question 4

% of lipids and proteins of the classes of LP particles?

Answer 4

Chylomicrons: 99% lipid, 1% protein
VLDL: 92 to 8
LDL: 80 to 20
HDL: 50 to 50

Question 5

Apo AI

Answer 5

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

Question 6

Apo B-100

Answer 6

Involved in VLDL assembly and secretion

Question 7

Apo CII

Answer 7

Activator of LPL

Question 8

Apo CIII

Answer 8

Inhibitor of LPL

Question 9

Apo E

Answer 9

Acts as “reuptake;” Is a ligand for binding several lipoproteins to the LDL receptor; “recognition”

Question 10

Chylomicron characteristics

Answer 10

• Is the least dense of lipoproteins
• Contains the most TAGs
• Has Apo B-48, Apo E and Apo CII

Question 11

VLDL characteristics

Answer 11

• Contains TAG and cholesteryl esters in high concentrations

- Has Apo B-100, Apo CI, Apo CIII and Apo E

Question 12

IDL characteristics

Answer 12

• Results from significant amount of TAGs removed from VLDL

- Contains Apo B-100, Apo CI, Apo CII, Apo CIII and Apo E

Question 13

LDL characteristics

Answer 13

• Produced by removal of TAGs from VLDL
• Is enriched in cholesterol / cholesteryl esters
• Apo B-100 is major protein

Question 14

HDL characteristics

Answer 14

• Produced from enzymatic conversion of LDL and VLDL cholesterol to cholesteryl esters

Question 15

PCSK9

Answer 15

• Is a protease that degrades the LDL receptor after uptake of receptor-LDL complex
• Reduces [LDL receptors] in the blood

Question 16

Action of LPL

Answer 16

Digests TGs of chylomicrons to fatty acids (FAs) and glycerol

Question 17

Synthesis, processing and secretion of VLDL

Answer 17

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

Question 18

Elevations in plasma TG are usually a result of…

Answer 18

…increased VLDL levels!

Question 19

Perilipins surround…

Answer 19

…the TGs that are stored within cardiomyocytes in lipid droplets

Question 20

Perilipins role?

Answer 20

Modulate the actions of ATGL, which removes the first fatty acid from triglyceride

Question 21

After ATGL removes the FFA, the second and then final FAs are removed by…

Answer 21

…HSL and then MGL. These FAs then complex with CoA via ACSL

Question 22

In a pro-inflammatory state, enlarged adipocytes produce…

Answer 22

…monocyte chemotaxis protein (MCP-1), attracting macrophages to the tissue

Question 23

What do macrophages, attracted to adipocytes, do?

Answer 23

They produce TNF alpha, favoring the export of FAs to muscle.

Question 24

What does ectopic lipid do, regarding GLUT 4?

Answer 24

Interferes with GLUT 4 movement to the myocyte surface, producing INSULIN RESISTANCE

Question 25

Action of fibrates on the liver

Answer 25

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

Question 26

TZD (Thiazolidinedione) drug effects?

Answer 26

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

Question 27

Free cholesterol affects what 3 proteins?

Answer 27

• Induces ACAT (increase intracellular storage)
• Represses HMG-CoA (decreased cholesterol biosyn)
• Reduces synthesis / speeds up degradation of LDL receptors

Question 28

Role of ABCA1 (carrier of cholesterol)

Answer 28

ABCA1 and ApoA-I (nascent HDL) combine. If ABCA1 is defective, HDLs cannot form (Tangier dx)

Question 29

Cellular responses to excess plasma membrane cholesterol

Answer 29

• 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

Question 30

Role of LCAT?

Answer 30

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

Question 31

Increasing TG will (increase/decrease) [HDL]

Answer 31

Decrease!

Question 32

How do HDLs protect against cardiovascular disease?

Answer 32

• Promotes efflux of cholesterol from macrophages
• Inhibits the oxidative modification of LDLs
• Inhibits vascular inflammation and inhibits thrombosis

Question 33

Role of SR-BI (Scavenger receptor B I)?

Answer 33

Uptakes HDL into the tissue

Question 34

CETP (CE and TG transfer) transforms _____ back to _____

Answer 34

HDL2 is transformed back to HDL3

Question 35

Exercise decreases catabolism of HDL and thus, increases HDL levels. How?

Answer 35

• 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