L14 Cholesterol and Lipoprotein Metabolism

Question 1

What is the composition of a triglyceride?

Answer 1

Glycerol backbone and three fatty acids

Question 2

What is the composition of a phospholipid?

Answer 2

Two fatty acids attached to glycerol and phosphate with a variable head group

Question 3

What are some roles of cholesterol? (good and not so good) (3)

Answer 3

• Structural component of cell membrane for cell integrity and fluidity
• Precursor of steroid hormones, vitamin D and bile acids
• Accumulation in arteries leading to CHD and stroke

Question 4

Where is cholesterol mainly synthesised?

Answer 4

Liver and intestine, however can be synthesised in all cells

Question 5

What is cholesterol synthesis controlled by? (3)

Answer 5

• Dietary intake
• Cholesterol levels
• Hormones

Question 6

What condition do ‘statins’ treat?

Answer 6

Hypercholesterolaemia

Question 7

How are cholesterol levels normally balanced?

Answer 7

Balance between intake, synthesis, use, reabsorption and excretion

Question 8

What is HMG-CoA reductase?

Answer 8

A rate limiting enzyme to control cholesterol synthesis

Question 9

What is the structure of a lipoprotein?

Answer 9

Polar surface with phospholipids, cholesterol and proteins
Non-polar lipid core with TGs and cholesteryl esters

Question 10

What is the main component of chylomicrons? Is it the highest or lowest density?

Answer 10

Triglycerides
Lowest density due to its high fat and low protein content

Question 11

What is the main component of VLDL?

Answer 11

Triglycerides

Question 12

What is the main component of LDL?

Answer 12

Cholesterol

Question 13

What is the main component of HDL?

Answer 13

Protein

Question 14

Where are chylomicrons produced?

Answer 14

Inside enterocytes

Question 15

Where are VLDLs produced?

Answer 15

In the liver from chylomicron remnants and lipids

Question 16

How are LDLs produced?

Answer 16

From VLDL (via IDL) after lipoprotein lipase removes triglycerides

Question 17

Where are HDLs produced?

Answer 17

Initiated in the liver but mature in circulation

Question 18

What apo-lipoporotein is associated with HDL?

Answer 18

apoA-I

Question 19

What apo-lipoporotein is associated with LDL and VLDL?

Answer 19

apo-B100

Question 20

What apo-lipoporotein is associated with chylomicrons and chylomicron remnants?

Answer 20

apoE

Question 21

What is the main function of lipoproteins? (1)
What are its three pathways? (3)

Answer 21

• Used for transporting lipids
• Exogenous pathway - digestive system to liver
• Endogenous pathway - liver to other tissues
• Reverse transport - from tissues back to the liver

Question 22

What are functions of apolipoproteins? (2)

Answer 22

• Helping stabilise lipoproteins
• Interact with receptors on cell surfaces

Question 23

How does the exogenous lipid transport pathway work? (4 steps)

Answer 23

• Dietary lipids are packaged into chylomicrons inside enterocytes
• Chylomicrons are absorbed into the lymphatic system via lacteals
• Then enter the bloodstream via thoracic and right lymphatic ducts
• Remodelling of chylomicrons

Question 24

How do chylomicrons work? (4 steps)

Answer 24

• Chylomicrons interact with capillaries of muscle and adipose tissue
• Lipoprotein lipase hydrolyses TGs
• FAs and glycerol enter the cell for storage or fuel
• Converted into chylomicron remnants that travel back to the liver

Question 25

How does the VLDL lipid transport pathway work? (3 steps)

Answer 25

- Liver produces VLDLs which carry TGs and cholesteryl esters to tissues - Lipoprotein lipase removes TGs from VLDL to cells - Removal of TGs result in VLDL remnants which are mostly returned to the liver

Question 26

How is LDL formed? (3 steps)

Answer 26

- Remaining VLDL remnants in circulation become IDLs - Some IDLs are reabsorbed by the liver via LDL receptor - Remaining IDLs are hydrolysed by hepatic lipase which forms LDLs

Question 27

What lipoprotein is the main lipoprotein that transports cholesterol to cells in the body?

Answer 27

LDL

Question 28

How is LDL taken up by cells? (3 steps)

Answer 28

- LDL's apoB-100 binds to LDL receptor (LDLR) on the cell surface - LDLR-mediated endocytosis occurs; cell membrane encloses LDL into a vesicle which enters the cell - LDL is hydrolysed and cholesterol is released

Question 29

What is the chain of events from an oversupply of cholesterol? (6)

Answer 29

- Increased intracellular cholesterol - Inhibited cholesterol synthesis - Inhibited LDLR synthesis - Down-regulation of LDLR synthesis - Decreased LDL uptake - Hypercholesterolaemia

Question 30

What happens when there is excess LDL? (2)

Answer 30

- LDL accumulates in the arterial walls - May become oxidised leading to atheroma formation

Question 31

How do HDL particles fill with cholesterol? (1)

Answer 31

By ApoAI binding to ABCAI

Question 32

Describe HDL maturation (3 steps)

Answer 32

- HDL binding to ABCAI causes efflux of free cholesterol and phospholipids - Free cholesterol is esterified by lecithin-cholesterol acyltransferase (LCAT) and stored as cholesterol esters - Cholesterol esters move to hydrophobic core of particle and produces a mature HDL

Question 33

Describe HDL reverse transport - direct pathway (2)

Answer 33

- HDL particles circulate and remove cholesterol from cells, and pick up phospholipids via phospholipid transport protein (PLTP) - HDL then delivers cholesterol to the liver or steroidogenic organs such as adrenals, testes and ovaries

Question 34

a) What does HDL use in its indirect transport pathway? (1) b) What does it promote the transfer of? (2) c) Why is this pathway beneficial? (1)

Answer 34

a) Cholesteryl ester transfer protein (CETP) b) Promotes the transfer of: - TG from VLDL and LDL to HDL - Cholesterol esters from HDL to VLDL and LDL c) Enables HDLs to stay in circulation to remove cholesterol