Membranes and Lipids 3

Question 1

What is the structure and classification of lipoproteins?

Answer 1

Lipoproteins have a phospholipid bilayer embedded with cholesterol and apolipoprotein. Encapsulated in lipoproteins are cholesterol and triglycerides.

Lipoproteins are categorised into:

• Chylomicrons - Carry dietary cholesterol. The least dense and largest lipoprotein.
• VLDL - Carry cholesterol from the liver to peripheral tissues.
• LDL - Carry cholesterol from the liver to peripheral tissues. The main carrier of cholesterol in the body.
• HDL - Carry cholesterol from the peripheral tissues to the liver. Seen as the ‘healthy cholesterol’.

Question 2

What is the role of cholesterol in atherosclerosis?

Answer 2

High cholesterol levels can lead to clogged arteries that come from a process known as atherosclerosis or hardening of the arteries. Plaques begin in artery walls and grow over years. The growth of cholesterol plaques slowly blocks blood flow in the arteries. Worse, a cholesterol plaque can suddenly rupture. The sudden blood clot that forms over the rupture then causes a heart attack or stroke.This can increase the chances of an MI or a stroke.

Question 3

How is cholesterol synthesised?

Answer 3

The enzyme HMG-CoA is converted to mevalonate through the enzyme HMG-CoA reductase. Mevalonate is then converted to IPP, which is converted to FPP, which is converted to Squalene. Squalene is the precursor of cholesterol.

Question 4

How do statins work?

Answer 4

Statins inhibit HMG-CoA reductase and therefore reduce the concentration of mevalonate. As a result, statins reduce the amount of cholesterol synthesised.

Question 5

How have statins been shown to be pleiotropic?

Answer 5

Statins have shown to have more beneficial effects than expected. They have shown to reduce the chance of stoke and MI in patients with normal cholesterol. They also improve endothelial dysfunction, have antioxidant properties, inhibition of inflammatory responses and stabilise atherosclerotic plaques.

This is as mevalonate is a precursor of isoprenoids, Rho and Ras. The pleiotropic properties may be due to the reduced Rho concentration. Rho has been shown to have a large effect on cardiovascular events. They increase thrombosis, inflammatory molecules and adhesion molecules.

Question 6

What are apolipoproteins? What are the classifications?

Answer 6

Apolioproteins are ligands that bind to the receptors on the target cells. They insure that the right lipid is taken up into the cell. Each lipoprotein has a unique apolipoprotein and so is recognisable by the cells. Apolipoproteins are synthesised in the intestine in response to dietary uptake. The types of apolioproteins include:

• apoA - Found on HDL
• apoB - Found on LDL; therefore the principle receptor in the uptake of cholesterol into peripheral tissues.
• apoC - Activates enzymes that can be transferred across lipoproteins and activates enzymes important in lipid metabolism.
• apoE - Can stabilise VDL for cellular uptake

Question 7

Using angiotensin II as an example, how can the signal cause an effect on the cell?

Answer 7

Angiotensin II binds to the AT1R (Angiotensin II Type 1 Receptor). This activates the Gq protein. The activation of this protein, activates Phospholipase C. The activation of this enzyme increases the concentration of DAG and IP3. DAG activates protein kinase C. IP3 leads to the increase in intracellular calcium concentration which goes onto activate kinases.

Question 8

Using Acetylcholine (and the Muscarinic receptor) as an example, how can the signal cause an effect on the cell?

Answer 8

Acetylcholine binds go the Muscarinic receptor. This activates the Gi protein. This decreases the concentration of cAMP. cAMP can then activate protein kinase A.

Question 9

Using nitric oxide as an example, how can the signal cause an effect on the cell?

Answer 9

Nitric oxide - and other gasotransmitters - can diffuse straight across the bilayer. These can then go onto activate granulate cyclase, increasing the concentration of cGMP. cGMP can then activate protein kinase C.

Question 10

Using adrenaline as an example, how can the signal cause an effect on the cell?

Answer 10

Adrenaline binds to the adrenergic receptor. This activates the Gs protein. Gs therefore increases the concentration of cAMP which can then activate protein kinase A.

Question 11

What is the Phosphodiesterase 5 inhibitor that improves erectile function?

Answer 11

Sildenafil