Cholesterol

Question 1

Describe the first step of cholesterol synthesis.

Answer 1

1. Synthesis of ketone body until HMG-CoA
2. HMG-CoA is reduced into mevaloate by HMG-COA reductase. This reaction is coupled with the oxidation of 2 molecules of NADPH and H+ into NADP+

Question 2

Describe the second step of cholesterol synthesis.

Answer 2

Mevaloate is phosphorylated three times to create 3-phospho-5-pyrophosphomevaloate.

Then this molecule undergoes decarboxylation and dephosphorylation to generate two active isoprenes.

The purpose of this step if to reduce mevaloate (6-carbon) into two active isoprenes (5-cabon)

Question 3

Describe the third step of cholesterol synthesis.

Answer 3

1. Two isoprenes are added together to form a 10-carbon molecule by prenyl trasnferase.
2. Another isoprene is added to the 10-carbon molecule to form a 15-carbon molecule by prenyl transferase.
3. Two 15-carbon molecules are added together to form a 30-carbon molecule called squalene by squalene synthase.

Question 4

Describe the fourth step of cholesterol synthesis.

Answer 4

An oxygen molecule is added into squalene to form an epoxide. This epoxide is then hydrolyzed to generate a hydroxyl group on carbon-3 by cyclase.

Cyclase then catalyzes 19 more steps to create cholesterol.

Question 5

During what period and what hormone activates HMG-CoA reductase?

Answer 5

During high levels of glucose, insulin is stimulated which activates HMG-CoA reductase.

Question 6

During what period and what hormone activates HMG-CoA reductase?

Answer 6

During low levels of glucose glucagon inhibits HMG-CoA reductase.

When cholesterol levels are high, oxysterol inhibits HMG-CoA reductase by stimulating proteolysis.

During low levels of ATP, AMPK inhibits HMG-CoA reductase.

Question 7

What is the function of oxysterol?

Answer 7

When cholesterol levels are high, oxysterol inhibits HMG-CoA and inhibits receptor-mediated endocytosis to prevent extracellular cholesterol from being transported inside the cell.

Question 8

How is cholesterol transported inside the cells or blood?

Answer 8

Cholesterol activates ACAT which allows cholesterol to be stored as cholesteryl esters.

Question 9

What happens to SCAP/SREBP during high levels of cholesterol?

Answer 9

SCAP/SREBP are retained together in the ER, bound to Insig

Question 10

What happens to SCAP/SREBP during low levels of cholesterol?

Answer 10

1. Ubiquitin degrades Insig
2. SCAP/SERBP are transferred to the Golgi where proteases release the regulatory domain of SERBP
3. The regulatory domain of SERBP enter the nucleus where it activates synthesis of cholesterol.

Question 11

A patient has a mutation that inhibits proteolysis of the 7-dehydrocholesterol. What are the consequences of this?

Answer 11

Proteolysis of 7-dehydrocholesterol initiates the synthesis of vitamin D3, an important component for calcium uptake. Meaning the patient is likely to have a deficiency in calcium.

Question 12

What are the four types of lipoproteins involved in lipid trnasport?

Answer 12

1. chylomicrons
2. VLDL
3. LDL
4. HDL

Question 13

Which type of lipoproteins is involved in transporting dietary lipids?

Answer 13

chylomicrons

Question 14

Which lipoprotein is the densest? Why?

Answer 14

HDL - because it’s the one with the highest protein mass

Question 15

Which lipoproteins is the largest and least dense? Why?

Answer 15

Chylomicrons - because it has the least protein mass and most TAGs

Question 16

A patient has developed a type of cardiovascular disease. Which lipoproteins is likely associated with this disease?

Answer 16

LDL

Question 17

What is likely to happen if LDL receptors cannot bind to ApoB-100 on LDL particles?

Answer 17

Endocytosis is likely inhibited which leads to excess of LDL and subsequent cardiovascular diseases.

Question 18

Atherosclerosis occurs due to excess circulation of LDL. What does this means in terms of HDL?

Answer 18

That HDL is inhibited and therefore it cannot clear LDL through reverse transport.

Question 19

When would AMPK be activated or inhibited?

Answer 19

It will be activated during low levels of ATP (or high levels of AMP) and inhibited during high levels of ATP.