Cholesterol Metabolism

Metabolism of cholesterol following the syllabus of Medical Biochemistry of MBBS course

1. CHOLESTEROL METABOLISM

2. CHOLESTEROL

3. Functions of Cholesterol

4. Structure of Cholesterol

5. Cholesterol Biosynthesis Virtually all tissues containing nucleated cells are capable Occurs in ER and cytosol Site: Liver (10%), Intestine (10%), Adrenal cortex, Reproductive tissues, Skin All the carbon atoms of cholesterol are derived from acetyl CoA Requirements: Acetyl CoA- 18 moles ATP- 36 moles NADPH- 16 moles

6. Steps of De Novo Cholesterol Synthesis Step 1—Biosynthesis of Mevalonate (6C) Step 2—Formation of Isoprenoid Units (5C) Step 3—Six Isoprenoid Units Form Squalene (30C) Step 4—Formation of Lanosterol (30C) Step 5—Formation of Cholesterol (27C)

7. 2 Acetyl-CoA Acetoacetyl -CoA HMG-CoA Mevalonate Several steps Cholesterol First 2 steps are similar as ketone body synthesis But KB synthesis occurs in mitochondria

8. HMG-CoA reductase Rate limiting enzyme Present in endoplasmic reticulum Regulated by- Feedback control (mevalonate, cholesterol) Hormonal regulation Insulin, thyroxin (+) Drugs (Statins) Glucagon, glucocorticoid (-) Bile acids, fasting

9. HMG-CoA reductase (active) HMG-CoA reductase (Inactive) Acetyl-CoA HMG-CoA Mevalonate CHOLESTEROL Insulin Glucagon Increased caloric intake, Thyroid hormone Bile acids, glucocorticoids, Dietary cholesterol P Dephosphorylation Phosphorylation + + + - Regulation of de novo synthesis of cholesterol

10. Excretion of Cholesterol Cannot be destroyed by oxidation to CO 2 and H 2 O, because of absence of enzyme capable of catabolising the steroid nucleus 50% is converted to bile acid Cholesterol is excreted in faeces About 1gm of cholesterol is eliminated from the body per day (C-0.6g/d; bile acid-0.4 g/d)

11. BLOOD CHOLESTEROL

12. Factors affecting serum cholesterol level Hereditary factors Diet Beneficial- Unsaturated fats ( ω₆ , ω₃ FA) Harmful- Saturated fat, sucrose, fructose Lifestyle- High blood pressure, smoking, male gender, obesity, lack of exercise, soft drinks, emotional stress Hypolipidemic drug (atorvastatin, simvastatin, Fluvastatin)- when diet change fail

13. Disorder of Cholesterol Metabolism

14. Thank You