Lecture 13 - Cholesterol Biosynthesis Mechanism

Question 1

Briefly describe the mechanism of cholesterol biosynthesis

Answer 1

1) Condensation of 3 acetate units to form the 6-carbon mevalonate
2) Conversion of mevalonate to activated isoprene units
3) Polymerization of six 5-carbon isoprene units to form the 30-carbon linear squalene
4) Cyclicization of squalene to form the four rings of the steroid nucleus, followed by several oxidations/removal reactions to produce cholesterol

Question 2

Step 1

Answer 2

Acetyl-CoA -> acetoacetyl-CoA

Question 3

Enzyme of step 1

Answer 3

Beta-ketoacyl-CoA thiolase

Question 4

Cofactor of step 1

Answer 4

Acetyl-CoA -> CoA-SH

Question 5

Step 2

Answer 5

Acetoacetyl-CoA -> hydroxymethyl glutaryl-CoA

Question 6

Enzyme of step 2

Answer 6

HMG-CoA synthase

Question 7

Cofactor of step 2

Answer 7

Acetyl-CoA -> CoA-SH

Question 8

Step 3

Answer 8

Hydroxymethyl glutaryl-CoA -> mevalonate

Question 9

Enzyme of step 3

Answer 9

HMG-CoA reductase

Question 10

Cofactor of step 3

Answer 10

• 2 NADPH + H+ -> 2 NADP+

- CoA-SH out

Question 11

How many acetyl-CoA molecules are used in the first part of cholesterol biosynthesis?

Answer 11

3

Question 12

What can inhibit cholesterol biosynthesis?

Answer 12

• Cholesterol metabolite

- Glucagon

Question 13

What can activate cholesterol biosynthesis?

Answer 13

Insulin

Question 14

What is the rate limiting step of carbohydrate biosynthesis?

Answer 14

Part 1 (synthesis of mevalonate)

Question 15

Step 4

Answer 15

Mevalonate -> delta3-isopentenyl pyrophosphate

Question 16

Enzyme of step 4

Answer 16

3 enzymes

Question 17

Cofactor of step 4

Answer 17

3 ATP -> 3 ADP + 3 Pi

Question 18

Step 5

Answer 18

Delta3-isopentenyl pyrophosphate -> delta2-isopentenyl pyrophosphate

Question 19

Enzyme of step 5

Answer 19

Isopentenyl pyrophosphate isomerase

Question 20

Cofactor of step 5

Answer 20

None

Question 21

What occurs in step 5?

Answer 21

Double bond is moved

Question 22

_____ are the building blocks for larger terpenes and steroids

Answer 22

Isopentenyl pyrophosphates

Question 23

Step 6

Answer 23

Delta2-isopentenyl pyrophosphate and delta3-isopentenyl pyrophosphate -> geranyl pyrophosphate

Question 24

Enzyme of step 6

Answer 24

Prenyl transferase

Question 25

Cofactor of step 6

Answer 25

PPi -> 2 Pi out

Question 26

Step 7

Answer 26

Geranyl pyrophosphate and delta3-isopentenyl pyrophosphate -> farnesyl pyrophosphate

Question 27

Enzyme of step 7

Answer 27

Prenyl transferase

Question 28

Cofactor of step 7

Answer 28

None

Question 29

Step 8

Answer 29

Farnesyl pyrophosphate -> squalene

Question 30

Enzyme of step 8

Answer 30

Squalene synthase

Question 31

What are monoterpenes formed from?

Answer 31

Geranyl pyrophosphate

Question 32

What are ubiquinones formed from?

Answer 32

Farnesyl pyrophosphate

Question 33

What are sesquiterpenes formed from?

Answer 33

Farnesyl pyrophosphate

Question 34

What are diterpenes formed from?

Answer 34

Farnesyl pyrophosphate

Question 35

What are carotenoids formed from?

Answer 35

Diterpenes

Question 36

What are triterpenes formed from?

Answer 36

Squalene

Question 37

What is cholesterol formed from?

Answer 37

Squalene

Question 38

Which enzyme and cofactor convert cholesterol to cholesteryl ester?

Answer 38

• Acyl-CoA-cholesterol acyl transferase

- Fatty acyl-CoA -> CoA-SH

Question 39

Which enzyme converts phosphatidylcholine to cholesteryl ester and lysolecithin?

Answer 39

Lecithin-cholesterol acyl transferase

Question 40

Where are fatty acyl cholesterols and lysolecithin found and what is their function?

Answer 40

• Found in lipoproteins

- Important in removing cholesterol from the body