Lecture 7 - Lipid Control in Health and Disease

Question 1

How were different lipoproteins named?

Answer 1

By where they banded on an equilibrium density gradient centrifuge tube.

Question 2

Implication of greater lipoprotein density

Answer 2

More protein, less lipid

Question 3

Shape of lipoproteins

Answer 3

Spherical

Question 4

What are lipoproteins bound by?

Answer 4

A phospholipid monolayer

Question 5

LDL structure
1)
2)
3)

Answer 5

1) ApoB-100 protein
2) Phospholipid monolayer with unesterified cholesterols
3) Core of triaceylglycerols and cholesterol esters

Question 6

When does risk of heart attack significantly rise w/r/t blood cholesterol level

Answer 6

~5mmol/L

Question 7

Chylomicron structure
1)
2)
3)

Answer 7

1) Apolipoproteins (B-48, C-II, C-III)
2) Less cholesterol than LDL
3) More protein than LDL

Question 8

Where are chylomicrons formed?

Answer 8

Intestinal mucosa

Question 9

Role of chylomicrons

Answer 9

Carry TAGs from diet to tissues via the lymphatics and blood

Question 10

Cholesterol form on the surface of lipoproteins

Answer 10

Free (unesterified) cholesterol

Question 11

Are chylomicrons more or less dense than VLDL?

Answer 11

Less dense

Question 12

Lipoproteins that primarily carry TAGs in the blood

Answer 12

Chylomicrons, VLDL

Question 13

Lipoproteins that primarily carry cholesterol in the blood

Answer 13

LDL, HDL

Question 14

Three lipid transport systems

Answer 14

1) Exogenous
2) Endogenous
3) Reverse cholesterol transport

Question 15

Exogenous lipid transport
1)
2)
3)
4)
5)

Answer 15

1) Dietary fats broken down into free fatty acids, mono- and diacylglycerols by intestinal lipases (bile salts emulsify)
2) Breakdown products are taken up by mucosa, reformed into TAGs and incorporated into chylomicrons
3) Chylomicrons move through bloodstream and lymphatics into tissues
4) ApoC-II on chylomicron activates lipoprotein lipase on capillary wall. Lipoprotein lipase converts TAGs to free fatty acids and glycerol
5) Fatty acids enter cells, are either oxidised for energy or reesterified for storage
6) Chylomicrons depleted of TAGs (chylomicron remnants) are taken in the blood to the liver, where they are taken up by RME

Question 16

Endogenous lipid transport
1)
2)
3)
4)
5)

Answer 16

1) VLDL assembled in ER of hepatocytes on ApoB-100 scaffold
2) ApoE and ApoC-II associate with VLDL in the blood.
3) Lipoprotein lipase (activated by ApoC-II) converts TAGs to FFAs. This converts VLDL to IDL (intermediate-density lipoprotein).
4) ~50% of IDL taken up by liver via LDL receptor that recognises ApoE on IDL. ~50% of IDL sheds ApoE, becomes LDL.
5) ~70% of LDL is taken up by liver via LDL-R, ~30% enters muscle, adipocytes, adrenal glands.

Question 17

How does ApoB-100 help form VLDL?

Answer 17

Has binding sites for microsomal transfer protein (MTP) necessary for formation of VLDL

Question 18

Reverse cholesterol transport
1)
2)
3)
4)
5)

Answer 18

1) HDL starts as a disc of ApoA-1 (protein) and phospholipid
2) Free cholesterol is esterified, incorporated into HDL3
3) More esterified cholesterol binds to HDL, forming HDL2
4) CETP assists in the exchange of esterified cholesterol from HDL with TAGs from LDL and VLDL.
5) HDL interacts with SR-B1 in the liver, delivers TAGs to the liver.

Question 19

Why might high HDL levels correlate with less heart disease?

Answer 19

HDL in blood picks up excess free cholesterol from arterial walls, converts them to cholesteryl esters, delivers them to the liver where they are converted to bile.

Question 20

Where is ApoA-1 formed?

Answer 20

In the liver and intestine

Question 21

Protein disc that forms core of HDL

Answer 21

ApoA-1

Question 22

Medications that can increase blood TAGs
1)
2)
3)

Answer 22

1) Beta blockers
2) Immunosuppressants
3) Oestrogen replacement

Question 23

Medications that can decrease TAG clearance from blood

Answer 23

1) Beta blockers

2) Protease inhibitors

Question 24

What effect does hyperthyroidism have on TAG levels in blood?

Answer 24

Reduces TAG clearance, increases TAG formation

Question 25

Genetic factors that can lead to increased blood TAG levels
1)
2)

Answer 25

1) ApoB-100 mutations can lead to increased VLDL

2) Lipoprotein lipase or ApoC-II mutations can reduce TAG breakdown

Question 26

Atherogenic

Answer 26

Can cause atherosclerotic plaques

Question 27

Examples of dislipidaemias
1)
2)
3)
4)

Answer 27

1) Hypercholesterolaemia
2) Increased LDL
3) Hypertriglyceridaemia
4) Decrease in HDL

Question 28

How can metabolic syndrome cause dyslipidaemias?

Answer 28

Alterations to HDL and LDL particles.

Abnormal LDL are more atherogenic. Small, dense, TAG-rich, oxidised, glycated.

Question 29

HDL in metabolic syndrome and T2DM
1)
2)

Answer 29

1) Hypertriglyceridaemia can lead to increased HDL catabolysis
2) increased glycation of HDL could interfere with cholesterol efflux from cells and cholesterol reverse transport

Question 30

How can hypertriglyceridaemia lead to increased HDL catabolysis?

Answer 30

With more TAGs, CETP transfers more TAGs from VLDL and LDL to HDL.

TAG-rich HDL is degraded more by hepatic lipase

Question 31

Development of atherosclerosis
1)
2)
3)
4)
5)
6)
7)

Answer 31

1) Damage to endothelium (EG: by oxidised LDL)
2) Endothelial cells, smooth muscle cells, macrophages release oxidants, resulting in more oxidised LDL
3) Ox-LDL leads to increased expression of monocyte chemotaxis factor, macrophage colony stimulating factor, P-selectin on endothelial wall
4) Monocytes enter tissue, differentiate to macrophages, release ROS, leading to highly oxidised LDL
5) Macrophages take up highly-ox LDL in an unregulated way. Form foam cells.
6) Foam cells attract lymphocytes, leukocytes and smooth muscle cells, forming a fatty streak on blood vessel wall
7) Fibrous cap forms over fatty plaque