1. Lipoprotein
Structures, Function and Metabolism
(2)

2. Lipoproteins in plasma
Density Mobility Component
CM CM TG rich
VLDL Pre-b-lipoprotein TG rich
LDL b-lipoprotein Cholesterol rich
HDL a-lipoprotein Cholesterol/protein rich

3. Chylomicron
Transport dietary lipids from the intestine to the peripheral tissues

4. VLDL – IDL - LDL
VLDL function: Deliver TG from liver to peripheral tissue cells
LDL function: Deliver Cholesterol from live to peripheral tissue cells

5. Metabolism of VLDL and LDL

6. LDL
Cholesterol rich
Can be taken up either by the peripheral tissues or by the liver
LDL is taken up by LDL receptor through apoB100/LDL receptor interaction.
After internazation, the LDL is digested by lysosomal enzymes. The cholesterol is released and the receptor recycles back to the membrane.
LDL function: Deliver cholesterol from liver to peripheral tissue cells.

7. LDL receptor (839 aa) extracellular domain is
responsible for apoB100/apoE binding
intracellular domain is
responsible for clustering of LDL receptors into clathrin- coated pit region of plasma membrane
LDL receptors exist in most peripheral tissues and in the liver.

8. Michael S. Brown and Joseph L. Goldstein discovered LDL-receptor.
1985 Nobel prize in Medicine

9. LDL cholesterol levels are positively related to risk of cardiovascular disease
Therefore, cholesterol in LDL has been called “bad cholesterol”
Defects in the LDL receptor leads to familial hypercholesterolemia

10. Familial Hypercholesterolemia
LDL-receptor deficiency
420 different mutations identified
LDL-receptor activity: 0-25% of normal
Classes of LDL-receptor mutations
1 – no receptors
2 – blockage of receptor from ER to Golgi Apparatus
3 – receptor does not bind LDL normally
4 – receptor does not accumulate in clathrin-coated pit
5 – receptor fails to release LDL after internalization and does not recycle to cell surface

11. Metabolism of HDL

12. HDL
HDL are synthesized in the liver and intestine as a small disc-like particle.
Proteins on the surface of HDL: apoAs, apoCs, apoE, CETP，LCAT.
Nascent HDL acquires cholesterol in peripheral tissues.

13. HDL The cholesterol is esterificated by LCAT (lecithin cholesterol
acyltransferase) associated with the particle. This reaction is
activated by apoA-I
The cholesterol ester move to the hydrophobic core of the
particle and particle becomes spherical.

14. HDL
HDL particles bind to SRB1 receptors (scavenger receptor type B1) on the liver and are taken into the cells.
HDL particles are also a reservoir for apolipoproteins (especially apoE & apoCII）
Some of the CE in HDL is transferred from HDL to other lipoproteins by cholesterol ester transfer protein （CETP）

15. HDL
HDL salvage excess cholesterol from cells and reverse-transport cholesterol from peripheral cells to the liver for excretion
HDL cholesterol levels are inversely related to risk of cardiovascular disease
Therefore, cholesterol in HDL has been called “good cholesterol”

16. Main Functions of Lipoproteins
CM: transfer exogenous lipids (dietary fat) from intestine to peripheral tissues.
VLDL-LDL: transfer endogenous lipids from liver to peripheral tissues.
HDL: reverse cholesterol transport from peripheral tissues to liver.

17. Lipoproteins (a) Another kind of atherogenic lipoprotein.
Consist of LDL and a protein designated as apo(a)
The apo(a) is covalently linked to apoB-100 by a disulfide linkage
High risk association with premature coronary artery disease and stroke.

18. Hyperlipoproteinemia

19. Fredrickson classification of hyperlipoproteinemia
Type I (hyperchylomironemia):
Increased CM
Type II-A (hyper-b-lipoproteinemia):
Increased LDL
Receptor deficiency or polygenic disorder.
Type II-B:
Increased VLDL + LDL
Increased production of VLDL and impaired LDL catabolism
Type III: (broad-b-lipoproteinemia)
Increased IDL, elevated cholesterol and triglycerides

20. Fredrickson classification
Type IV: (hyper-pre-b-lipoproteinemia)
Increased VLDL
Impaired VLDL catabolism
Type V:
Increased CM + VLDL
Reduced lipoprotein lipase

22. Where do we get cholesterol?
Our bodies make all the cholesterol we need.
We also get cholesterol from foods we eat. 22

23. Blood cholesterol levels increase by eating these products
Beef
poultry,
fish
milk,
eggs,
cheese,
yogurt, etc. 23

24. Why worry about cholesterol?
Blood cholesterol can stick to the sides of arteries.
Blockages can form.
It can lead to serious medical problems:
Heart attack and
Stroke. 24

25. What does my total cholesterol mean?
Normal
Less than 200 mg/dL
Borderline High
High
240 mg/dL or higher
mg/dL 25

26. HDL Cholesterol 26 Optimal: 60+ mg/dL for both males and females
At Risk for Heart Disease:
Women: less than 50 mg/dL
Men: less than 40 mg/dL 26

27. LDL Cholesterol
Optimal
Less than 100 mg/dL
Near or above Optimal
mg/dL
Borderline High
mg/dL
High
mg/dL
Very High
190+ mg/dL
Now let’s examine where we want LDL cholesterol levels to be for both men and women. Remember, LDL cholesterol is considered the bad cholesterol, so we want it as low as possible.
Any level below 100mg/dL is optimal, and levels between mg/dL are near or above optimal. Levels between mg/dL are considered borderline high. Levels between mg/dL are considered high, and levels above 190 mg/dL are considered very high.
There are many things you can do to reduce your LDL cholesterol levels if they fall in any of the high categories. 27

28. Triglycerides Now let’s discuss triglyceride levels.
Normal
Less than 150 mg/dL
Borderline High
mg/dL
High
mg/dL
Very High
500+ mg/dL
Now let’s discuss triglyceride levels.
Less than 150 mg/dL is normal and where you want to be. Between mg/dL is borderline high; mg/dL is high; and 500+ mg/dL is very high.
Remember, triglycerides are fats, and the lower the better! 28