Cholesterol Synthesis & Transport

Question 1

Cholesterol is an amphipathic molecule. What does this mean?

Answer 1

It contains both hydrophilic and hydrophobic portions.

Question 2

What is the role of LDL?

Answer 2

Transporting cholesterol to tissues.

Question 3

What is the role of HDL?

Answer 3

Transporting cholesterol from tissues to liver.

Question 4

What is atherosclerosis?

Answer 4

Narrowing of arteries associated with lipoprotein metabolism.
Damage to endothelial cells, LDL & platelet migration to the damage, recruitment of smooth muscle cells & macrophages, activation of macrophages, formation of foam cell (beginning of plaque formation). More LDL, more foam cells, more plaque.

Question 5

What are the 5 stages of cholesterol synthesis?

Answer 5

1. Mevalonate
2. Activated isoprene
3. 6 isoprenoid units
4. Cyclize squalene
5. Lose 3 methyl groups to form cholesterol

Question 6

What are the 4 ways that HMG-CoA reductase can be regulated?

Answer 6

Transcription - steroid response element
Rate of translation - mevalonate metabolites
Degredation - of enzyme
Phosphorylation - glucagon (x), insulin (+)

Question 7

What is the major difference between chylomicrons and LDL?

Answer 7

Chylomicrons transport dietary molecules & are the least dense but largest lipoproteins.
LDL transports cholesterol to tissues and stays in blood longer.

Question 8

Describe the LDL pathway of delivering cholesterol to cells.

Answer 8

Receptor binds apoB100 on LDL and undergoes receptor-mediated endocytosis. Receptor AND LDL are capsulated in an endosome. Endosome begins to split, segregating receptors (back to plasma mem) and then fusion of LDL with lysosome where the breakdown of LDL results in amino acids, fatty acids, and free cholesterol.

Question 9

What role does CETP play in HDL?

Answer 9

Cholesteryl ester transfer protein.
It facilitates the transfer of CEs from HDL to LDL so that CEs can be converted to free cholesterol via LDL pathway since HDL only off-loads via SR-BI rather than undergoing endocytosis.

Question 10

Diagram (or explain) enterohepatic circulation of cholesterol.

Answer 10

Cholesterol circulation within liver cells.

Cholesterol –>Bile salts (made in liver) –>Gall bladder (stored in) –> Small Intestine (released to solubilize fats) –> absorption –> Chylomicron remnants transported back to liver.

Question 11

What steroid is termed the hormone grandparent?

Answer 11

Pregnenolone

Question 12

Identify the major type of modification that distinguishes the steroids from each other.

Answer 12

Location of hydroxylations

Question 13

List the organs and their function in calcitrol synthesis.

Answer 13

Skin: UV catalyzed reaction
Kidneys: Detoxifies reactants before entering liver.
Liver: Forms calcitrol

Question 14

What are the three means of regulating cellular cholesterol levels?

Answer 14

HMG-CoA reductase - responds to cholesterol & precursors

ACAT (esterfies cholesterol)

LDL receptors - lower excess cholesterol

Question 15

What is the ultimate precursor for steroids?

Answer 15

Cholesterol