Pharmacology - Lipid Metabolism and Cardiovascular Disease

Question 1

Where do non-polar lipids travel in the blood?

Answer 1

Within lipoproteins e.g. HDL and LDL. Slide 3

Question 2

In atherosclerosis what are the LDL and HLD levels like?

Answer 2

Elevated LDL

Lowered HDL. Slide 3

Question 3

What are the 4 lipoproteins and what are the components of HLD, LDL particles and chylomicrons?

Answer 3

HDL, LDL, chylomicrons and VLDL.

HDL- ApoA1 and apoA2
LDL- ApoB100
Chylomicrons- ApoB48
Slide 4

Question 4

What do apoB containing lipoproteins do?

Answer 4

They deliver triglycerides to msucle for ATP biogenesis and adipocytes for storage.
Slide 5

Question 5

What is the life cycle of apoB containing lipoproteins?

Answer 5

Assembly- B100 in liver, B48 in intestine
Intravascular metabolism- Hydrolysis of triglyceride core
Receptor mediated clearance. Slide 5

Question 6

How do triglycerides and cholesterol enter cells?

Answer 6

Triglycerides are split by lipases into monoglyceride and 2 free fatty acids whcih diffuse into the cell and join together again.

Cholesterol has an enzyme (NPC1L1) which moves it across the membrane where is it esterified to become a cholesteryl ester. Slide 6

Question 7

How are chylomicrons and VLDL activated to deliver triglycerides to adipose and muscle tissue?

Answer 7

They are activated by HDL partciles transfering them apoCII and integrating it into their shell. Slide 8

Question 8

What happens during intravascular metabolism of ApoB lipoproteins?

Answer 8

ApoCII facilitate binding to cells and LPL hydrolyses their core triglycerides to enter the tissues which depletes the lipoprotein and chylomicron/VLDL remnents are left. Slide 9

Question 9

How are apoB containing lipoproteins cleared in the liver?

Answer 9

LPL has caused the lipoproteins to become enriched with cholesterol.

ApoCII is transferred back to HDL particles in return for ApoE which has high affinity for receptor mediated clearance.
They go to the liver and are metabolised by hepatic lipase.
Slide 10

Question 10

Where else can apoB containing lipoproteins be cleared and how?

Answer 10

By other tissue which express LDL receptor.
They cellular uptake depends on endocytosis and the cholesterol is released.
The released cholesterol inhibits cholesterol production by the hepatocyte and there is down regulation fo LDL receptor expression. Slide 11

Question 11

Why is LDL the ‘bad’ cholesterol?

Answer 11

It is the oxidised form of LDL (OXLDL) which causes atherosclerosis. Slide 12

Question 12

Why is HDL the ‘good’ cholesterol?

Answer 12

It has a key role of removign excess cholestrol from cells and transporting it to the liver.
It accepts excess cholesterol from plasma membrane cellls. Slide 13

Question 13

What is primary and secondary dyslipidaemia?

Answer 13

Primary is the excess of lipids through a combination of diet and genetic factors.
Secondary is due to the consequence of other diseases e.g. type II diabetes. Slide 14

Question 14

What are the Frederickson Classification of primary dyslipidaemia and which lipoproteins are elevated for each?

Answer 14

Type I - chylomicrons
Type IIa - LDL
Type IIb - VLDL + LDL
Type III - bVLDL
Type IV - VLDL
Type V - chylomicrons + VLDL. Slide 14

Question 15

What do statins do and how do they work?

Answer 15

Reduce LDL levels
They are competitive inhibitors to HMG-CoA which stops hepatocyte cholestrol synthesis and theres a compensatory expression in LDL receptors which increases cholesterol clearance. Slide 15

Question 16

What do fibrates do, how do they work and when are they used ?

Answer 16

They cause a decrease in triglycerides.
Act as agonists of receptors which enhance transcription of genes which code for LPL.
They are used when people have high triglyceride levels in the blood.
Slide 16