Cholesterol

Question 1

Step 1 of cholesterol formation and the enzymes
condensation

Answer 1

2 molecules of acetyl-CoA condense to form acetoacetyl CoA

E: cytoplasmic acetoacetyl CoA synthase (Thiolase)

Question 2

Step 2 of cholesterol formation and the enzymes
Production of HMG CoA

Answer 2

3rd molecule of acetyl CoA is added to produce
3-hydroxyl-3-methylglutaryl CoA (HMG CoA) (6 carbon skeleton)

E: HMG CoA synthase

Question 3

Step 3 of cholesterol formation and the enzymes
Synthesis of mevalonate

Answer 3

HMG CoA is reduced to mevalonate
2 molecules of NADPH are used as reducing agent release CoA

This step is irreversible reaction and rate limiting step and key regulated step in cholesterol synthesis

E: HMG CoA reductase

Question 4

Step 4A of cholesterol formation and the enzymes
Production of 5C unit

Answer 4

Mevalonate undergoes 2 step process where a phosphate group from ATP is transferred, resulting in 5-pyrophosphomevalonate with 6C

Pyrophosphate will helps to keep those water insoluble compound in solution

E: Kinase

Question 5

Step 4B of cholesterol formation and the enzymes and ATP required in this process
Production of 5C unit

Answer 5

5-pyrophosphomevalonate decarboxylated to form Isopentenyl pyrophosphate (IPP) (5C)

CO2 is remove

E: decarboxylase

required 3 ATP in total

Question 6

Step 5A of cholesterol formation and the enzymes
Condensation of 5C units

Answer 6

5C compounds condensed to form squalene (30C)
IPP(5C) IS ISOMERISED TO DIMETHYLALLYL PYROPHOSPHATE (DDP, 5C)

E: Isomerase

Question 7

Step 5B of cholesterol formation and the enzymes
Condensation of 5C units

Answer 7

CHEMICAL EQUATION:
DPP(5C) + IPP (5C) —-> Geranyl pyrophosphate (GPP, 10C)

WORD VERSION:
IPP & DPP undergo head to tail condensation, pyrophosphate group will displace to form geranyl phosphate

E: Transferase

Question 8

Step 5C of cholesterol formation and the enzymes
Condensation of 5C units

Answer 8

CHEMICAL EQUATION:
GPP (10C) + IPP (5C) —> Farnesyl pyrophosphate (FPP 15C)

WORD VERSION:
geranyl phosphate undergo another head to tail condensation with IPP yielding 15C intermediated farnesyl pyrophosphate (FPP)

E: Transferase

Question 9

Step 5D of cholesterol formation and the enzymes
Condensation of 5C units

Answer 9

CHEMICAL EQUATION:
FPP (15C) + FPP (15C) —> Squalene (30C) (1 NADPH required)

WORD VERSION:
2 molecules of farnesyl pyrophosphate (FPP) joined head-to head and remove both the pyrophosphate groups to form squalene

E: Squalene synthase

Question 10

Step 6 of cholesterol formation and the enzymes
Cyclisation

Answer 10

1) Squalene undergoes oxidation to form squalene epoxide
E: epoxidase
1O2 and NADPH are used

2) Squalene epoxide converted into lanosterol (30C)
first steroid compound produced
E: Cyclase

Question 11

Step 7 of cholesterol formation and the enzymes
Synthesis of cholesterol

Answer 11

Shortening of 30C compound to 27C compound

Removal of:
2 methyl groups at C-4
1 methyl group from C-14
Migration of= bonds from C-8 to C-5
Reduction of= bond between C-24 and C-25 to single bond

E: 7- dehydrocholesterol-7-reductase