10. Lipid Transport

Question 1

What are 2% of lipids bound to for transport and how are the other 98% transported?

Answer 1

2% are bound to albumin and the other 98% are carried as lipoprotein particles.

Question 2

Where is cholesterol synthesised?

Answer 2

In the liver.

Question 3

What is cholesterol a precursor to?

Answer 3

Steroid hormones and bile acids.

Question 4

How is cholesterol transported around the body?

Answer 4

As cholesterol esters.

Question 5

What are the five categories of lipoproteins according to their density?

Answer 5

Chylomicrons
VLDL - very low density lipoproteins
IDL - intermediate density lipoproteins
LDL - low density lipoproteins
HDL - high density lipoproteins.

Question 6

Which lipoproteins are main carriers of fat?

Answer 6

Chylomicrons and very low density lipoproteins.

Question 7

Which lipoproteins are main carriers of cholesterol esters?

Answer 7

IDL, LDL and HDL.

Question 8

When are chylomicrons present in the blood?

Answer 8

4-6 hours post meal.

Question 9

How can you tell if chylomicrons are present in the blood?

Answer 9

Take a sample and after using a centrifuge, it should be creamy if there are chylomicrons present.

Question 10

What are the six major classes of apolipoproteins (associated proteins)?

Answer 10

A, B, C, D, E and H.

Question 11

What are the important apolipoproteins for the four classes of lipoproteins?

Answer 11

apoB - VLDL, IDL and LDL

apoA - HDL

Question 12

What are the roles of apolipoproteins?

Answer 12

Structural - packaging water insoluble lipid

Functional - co-factor for enzymes, ligands for cell suface receptors.

Question 13

How are chylomicrons metabolised?

Answer 13

They’re loaded in the small intestine where apoB-48 is added before they enter the lymphatic system.
They travel to the thoracic duct and empty into the left subclavian vein, where they aquire two new apolipoproteins - apoC and apoE.
apoC binds lipoprotein lipases and adipocytes and muscle. Released fatty acids enter cells and deplete chylomicrons of their fat content.
When chylomicron TAG content is down to 20%, apoC detaches and the chylomicron is now called a chylomicron remnant.
The chylomicron remnants return to the liver. LDL receptors on hepatocytes bind apoE and the chylomicron remnants that were taken up by receptor mediated endocytosis.
Lysosomes release their remaining contents for use in metabolism.

Question 14

How are VLDLs metabolised?

Answer 14

VLDL is made in the liver for transport of TAGs to other tissues.
apoB100 is added during formation and apoC and apoE are added from HDL particles in the blood.
VLDL binds to lipoprotein lipase on endothelial cells in muscle and adipose and starts to have its TAG store depleted.
In the muscle, the release fatty acids are taken up and used in energy production.
In adipose, the fatty acids are used for resynthesis of TAGs and stored as fat.

Question 15

How are IDL and LDL metabolised?

Answer 15

They’re formed from VLDL -> IDL -> LDL
The TAG content of VLDL particles drops so VLDL particles dissociate from the LPL enzyme complex and return to the liver.
When VLDL content depletes to 30%, the particle becomes a short live IDL particle.
The IDL particle is taken up by the liver or rebinds to LPL enzyme to further deplete TAG content.
When TAG content is down to 10%, IDL loses apoC and apoE and becomes an LDL particle.

Question 16

What is the function of LDL?

Answer 16

To provide cholesterol form liver to peripheral tissues, the peripheral tissues have LDL receptors and take up LDL via receptor mediated endocytosis.

Question 17

Why are LDL not efficiently cleared by the liver?

Answer 17

Because they don’t have apoC or apoE.

Question 18

Why are LDL more susceptible to oxidative damage than VLDL and IDL?

Answer 18

Because LDL half life in the blood is far longer than VLDL or IDL. Oxidised LDL is taken up by macrophages and can be transformed to foam cells, which contribute to the formation of atherosclerotic plaques.

Question 19

How does LDL enter cells? Describe the process thoroughly.

Answer 19

By receptor mediated endocytosis.
Cells that require cholesterol have LDL receptors on their plasma membrane.
apoB-100 on LDL acts as a ligand for these receptors.
The receptor/LDL complex is taken into the cell by endocytosis.
The endosomes fuse with lysosomes that digest the complex and release cholesterol and fatty acids.
LDL-receptor expression is controlled by the cholesterol concentration in the cell.

Question 20

How are HDL synthesised?

Answer 20

In the liver or intestines or HDL particles bud off from chylomicrons and VLDL when they’re digested by LPL. Free apoA-I acquire cholesterol and phospholipid from other lipoproteins and cell membranes and form nascent HDL.

Question 21

How does nascent HDL mature into HDL?

Answer 21

Nascent HDL accumulate phospholipids and cholesterol from cells lining blood vessels.
The hollow core fill and particles become more globular in shape.

Question 22

How is HDL metabolised?

Answer 22

ABCA1 protein facilitates transfer of cholesterol to HDL,
cholesterol converted to cholesterol esters by LCAT. Mature HDL is taken up by the liver via specific receptors. Cells that require additional cholesterol utilise scavenger receptors to get cholesterol from HDL. HDL exchanges cholesterol ester for TAG with VLDL via cholesterol exchange transfer protein (CETP).

Question 23

What are the transport functions for the following?

a. Chylomicrons
b. VLDL
c. IDL
d. LDL
e. HDL

Answer 23

a. Transports dietary TAG from the intestine to tissues like adipose.
b. Transports of TAG synthesised in liver to adipose tissue for storage.
c. Short-lived precursor of LDL, transports cholesterol in the liver to the tissues.
d. Transports cholesterol synthesised in the liver to tissues.
e. Transports excess cholesterol from cells to the liver for disposal as bile salts and to cells require additional cholesterol.

Question 24

What is hyperlipoproteinaemia and what is it caused by?

Answer 24

Raised plasma level of one or more lipoprotein classes. Caused by over production or under removal. Due to defects in enzymes, receptors or apoproteins.

Question 25

What is type I hyperlipoproteinaemia caused by?

Answer 25

Defective lipoprotein lipase. Lead to chylomicrons in fasting plasma.

Question 26

What is type IIa hyperlipoproteinaemia caused by?

Answer 26

Defective LDL receptor. Associated with coronary artery disease.

Question 27

What is type IIb hyperlipoproteinaemia caused by?

Answer 27

Defect unknown. Associated with coronary artery disease.

Question 28

What is type III hyperlipoproteinaemia caused by?

Answer 28

Defective apoprotein apoE. Raised IDL and chylomicron remnants. Associated with coronary artery disease.

Question 29

What is type IV hyperlipoproteinaemia caused by?

Answer 29

Defect unknown. Associated with coronary artery disease.

Question 30

What is type V hyperlipoproteinaemia caused by?

Answer 30

Cause unknown. Raised chylomicron and VLDL in fasting plasma. Associated with coronary artery disease.

Question 31

What are clinical signs of hypercholesterolaemia?

Answer 31

Yellow patches on eyelids, nodules on tendon, obvious white circle around the eye. All caused by cholesterol depositions in the body.

Question 32

What is the first approach in treatment of hyperlipoproteinaemia?

Answer 32

Diet to reduce cholesterol and saturated lipids intake and lifestyle to increase exercise and stop smoking to reduce CVD risk.

Question 33

What is the second approach to treating hyperlipoproteinaemia?

Answer 33

Drugs. Statins reduce cholesterol synthesis by inhibiting HMG-CoA reductase, bike salt sequestrants bind bile salts in the GI tract and force the liver to produce more bile acids thus using more cholesterol.

Question 34

How are lipids transported in blood?

Answer 34

By carriers, needed as lipids are hydrophobic so are insoluble and can’t be transported in the blood.