Cholesterol

Question 1

What is an isoprene?

Answer 1

5C branched chain initiating unit for cholesterol synthesis

Question 2

What are terpenoids?

Answer 2

Isoprenoid with the presence of ring structures

Question 3

What is prenylation?

Answer 3

Attachment of farnesyl or geranylgeranyl groups to proteins to anchor them to the membrane

E.g. Ras

Farnesyl = 3 isoprene unites

Geranylgeranyl = 2x 2 isoprene unites

Question 4

What are some functions of cholesterol?

Answer 4

Stabilize cell membranes

Synthesize bile acids

Synthesize steroid hormones – Vit. D

Question 5

What is the nucleus of cholesterol?

Answer 5

Steroid 4-ring structure

Question 6

What two molecules combine to initiate cholesterol synthesis?

Answer 6

Acetoacetyl CoA and acetyl CoA

Question 7

What is the committed step of Cholesterol formation?

Answer 7

Synthesis of mevalonate via HMG-CoA reductase

Question 8

What is the role of squalene?

Answer 8

Intermediate in cholesterol synthesis that cyclizes to form the ring nucleus

Converted to cholesterol via many more steps

Question 9

Under what condition is cholesterol synthesized?

Answer 9

When energy is in excess

Question 10

What are the four mechanisms of HMG-CoA reductase regulation?

Answer 10

Sterol dependent

Sterol independent

Hormonal regulation

Inhibition by drugs

Question 11

Describe sterol dependent regulation

Answer 11

SCAP is bound to SREBP on the ER

Proteolytic cleavage via two proteases releases SREBP, which migrates to the nucleus and binds to DNA, initiating transcription of HMG CoA reductase

When cholesterol is present, it prevents migration of SCAP and SREBP to the golgi for processing

Question 12

Describe sterol independent regulation

Answer 12

Phosphorylation of HMG-CoA reductase inactivates it

Kinase is activated by glucagon, epinephrine, and AMP

Question 13

What type of drugs affect HMG-CoA reductase and how?

Answer 13

Statins - inhibit HMG-CoA reductase

Question 14

What is the physiological role of Chylomicrons?

Answer 14

Dietary fat transport

Question 15

What is the physiological role of VLDL?

Answer 15

Endogenous fat transport

Question 16

What is the physiological role of IDL?

Answer 16

LDL precursor

Question 17

What is the physiological role of LDL?

Answer 17

Cholesterol transport

Question 18

What is the physiological role of HDL?

Answer 18

Reverse cholesterol transport

Question 19

What is apoprotein B100?

Answer 19

Recognition molecule for the LDL receptor

Question 20

How are triglycerides and lipoprotein density related?

Answer 20

TG amount decreases as density increases

Question 21

What are the three isoforms of Apo E?

Answer 21

E2 - rarest form, one copy reduces risk of Alzheimer’s

E3 - most common, no influence

E4 - 20% of population, increases risk for Alzheimer’s

Question 22

How is cholesterol taken up by tissues?

Answer 22

LDL particle receptor mediated endocytosis

The receptor is a negatively charged glycoprotein concentrated in clathrin pits

Question 23

How is cholesterol degraded?

Answer 23

Sterol nucleus converted to bile acids

Cholesterol secreted into gall bladder

Used for synthesis of sterol hormones

Question 24

What is the rate-limiting step in steroid synthesis from cholesterol?

Answer 24

Formation of Prenenolone via Desmolase P450 enzyme

Question 25

What is formed from prenenolone during steroid synthesis?

Answer 25

Progestagens