4

Question 1

Sources of cholesterol

Answer 1

Diet- e.g. fish, liver, eggs

De novo synthesis

Liver - Major site of synthesis in mammals
Tightly regulated

Question 2

steps in chlestrol synth

Answer 2

Derived from acetyl CoA in a three-stage synthetic process

1) Synthesis of isopentenyl pyrophosphate (an inactivated isoprene that is the key building block of cholesterol)
2) Condensation of six molecules of isopentenyl pyrophosphate to form squalene
3) Cyclization of squalene and tetracyclic product is subsequently converted into cholesterol
1) occurs in cytoplasm, 2) and 3) occur in ER

Question 3

Stage One: Mevalonate Synthesis (activated by isopentenyl pyrophosphate)

Answer 3

Starts with formation of HMG-CoA from acetyl CoA and acetoacetyl CoA

Intermediate reduced to mevalonate

Mevalonate converted to isopentenyl pyrophosphate in 3 ATP requiring steps

Mevalonate synthesis COMMITED step

Catalysed by HMG-CoA reductase (important control site in cholesterol biosynthesis)

Question 4

How is HMG-CoA reductase regulated

Answer 4

1) Rate of synthesis of reductase mRNA
2) Rate of translation of reductase mRNA
3) Rate of reductase degradation
4) Phosphorylation of the reductase decreases its activity

Question 5

HMG-CoA as a target for drugs

Answer 5

Lovostatin discovered from fermentation broth from Aspergillus cereus

Question 6

another way to reduce cholesterol levels

Answer 6

Inhibit the intestinal reabsorption of bile salts. Bile salts are cholesterol derivatives that promote the absorption of dietary cholesterol and dietary fats

Question 7

How is cholesterol transported

Answer 7

Lipoproteins

Question 8

LDL

Answer 8

B100 (apolipoprotein): Cholesterol transport

Question 9

HDL

Answer 9

Reverse cholesterol transport

Question 10

Receptor mediated endocytosis

Answer 10

B100 (apolipoprotein) binds
LDL particle complex is internalized by endocytosis

Endosome is acidified (proton pump) which causes the receptor to release LDL cargo

Endosome fuses with lysosome (full of enzymes)

a. Protein component hydrolysed to free amino acids
b. Cholesterol esterols hydrolysed (lipase) to release free cholesterol

Question 11

what happens to cholesterol once released from LDL ting

Answer 11

i. Membrane biosynthesis

ii. Re-esterified and stored inside cell

Question 12

How does the LDL receptor relinquish its cargo on entering cell?

Answer 12

1) Extended or open stateàbind LDL
2) Closed stateàrelease LDL in endosome
3) Decrease in pH in the closed state

Question 13

Familial hypercholesterolemia

Answer 13

Lack LDL receptor so cholesterol builds up in plasma

kids die of coronary heart disease