CHOLESTEROL METABOLISM

Question 1

WHAT IS CHOLESTEROL?

Answer 1

CHOLESTEROL
- STEROID
- VERY HYDROPHOBIC COMPOUND

Question 2

STATE THE F(X) OF CHOLESTEROL

Answer 2

• COMPONENTS OF ALL CELL MEMBRANES
• PRECURSORS OF BILE ACIDS, STEROID HORMONES AND VITAMIN D
• STRUCTURAL COMPONENTS OF LIPOPROTEINS

Question 3

SOURCE OF HEPATIC CHOLESTEROL

Answer 3

1. DIETARY CHOLESTEROL (CM REMNANTS)
2. EXTRAHEPATIC CHOLESTEROL (VLDL AND HDL)
3. DENOVO SYNTHESIS

Question 4

DENOVO SYNTHESIS OF CHOLESTEROL

Answer 4

• PRIMARILY OCCUR IN LIVER
• CAN OCCUR IN THE ADRENAL CORTEX, OVARIES AND TESTES
• OCCUR IN THE CYTOPLASM AND HAVE AN ENZYME WHICH IS HMG COA REDUCTASE WHICH ACT AS A MAJOR CONTROLLER AND RATE LIMITING ENZYME
• OCCUR IN BOTH THE CYTOSOL AND ER
• REQUIRE ATP FOR PHOSPHATE GRP, OXYGEN AND ACETATE (PROVIDE CARBON)

Question 5

3 MAJOR STAGES IN DENOVO CHOLESTEROL SYNTHESIS.

Answer 5

1. SYNTHESIS OF HMG COA
2. SYNTHESIS OF MEVALONATE
3. SYNTHESIS OF CHOLESTEROL

Question 6

STATE THE REGULATIONS OF CHOLESTEROL SYNTHESIS.

Answer 6

1. STEROL DEPENDENT REGULATION BY GENE EXPRESSION (SREBP)
2. STEROL INDEPENDENT PHOSPHORYLATION/ DEPHOSPHORYLATION
3. HORMONAL REGULATION
4. INHIBITION BY DRUG

Question 7

DESC THE REGULATION OF CHOLESTEROL SYNTHESIS BY GENE EXPRESSION.

Answer 7

1. HIGH CHOLESTEROL
   - SREBP IS PREVENTED FROM TRANSLOCATION FROM THE ER TO THE GOLGI MEMBRANE
   - SREBP WILL NOT BIND TO THE RESPONSE ELEMENT IN THE HMG COA REDUCTASE
   - GENE TRANSCRIPTION OF THE HMG COA REDUCTASE IS REDUCED
   - LOW CHOLESTEROL SYNTHESIS
   - PROTEOLYTIC DEGRADATION OF THE HMG COA REDUCTASE
2. LOW CHOLESTEROL
   - SREBP IS TRANSLOCATED FROM THE ER TO THE GOLGI MEMBRANE
   - SREBP BIND TO THE RE IN THE HMG COA REDUCTASE
   - GENE TRANSCRIPTION OF THE HMG COA REDUCTASE INCREASES
   - HIGH CHOLESTEROL SYNTHESIS

Question 8

DESC THE REGULATION OF CHOLESTEROL SYNTHESIS WHEN THE GLUCOSE IS LOW.

Answer 8

WHEN THE GLUCOSE IS LOW:
- GLUCAGON ACTIVATION OF THE PROTEIN KINASE A
- PHOSPHORYLATION OF HMG COA REDUCTASE
- HMG COA REDUCTASE BECOME INACTIVE

Question 9

DESC THE REGULATION OF CHOLESTEROL SYNTHESIS WHEN THE GLUCOSE IS HIGH

Answer 9

WHEN GLUCOSE IS HIGH:
- INSULIN ACTIVATE THE PHOSPHOPROTEIN PHOSPHATASE
- DEPHOSPHORYLATION OF THE HMG COA REDUCTASE
- HMG COA REDUCTASE BECOME ACTIVE

Question 10

DESC THE REGULATION OF THE CHOLESTEROL SYNTHESIS WHEN THE ATP IS HIGH

Answer 10

ATP HIGH:
- DEACTIVATION OF THE AMP- ACTIVATED PROTEIN KINASE
- DEPHOSPHORYLATION OF THE HMG COA REDUCTASE

Question 11

STATE THE FATE OF THE CHOLESTEROL

Answer 11

1. CHOLESTEROL ESTER
2. BILIARY CHOLESTEROL
3. BILE ACIDS AND SALTS

Question 12

STATE THE EXAMPLE OF THE CHOLESTEROL LOWERING DRUGS

Answer 12

1. STATIN
2. EZETIMIBE
3. NIACIN
4. FIBRATES
5. BILE ACID RESINS