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Cholesterol metabolism

Cholesterol metabolism. Cholesterol. Found in animals 2gm/kg body weight Amphipathic in nature. Functions of cholesterol. Structural component of cell membrane Precursor of steroid hormones Structural part of lipoproteins Fatty acids are transported to liver as cholesteryl esters.

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Cholesterol metabolism

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  1. Cholesterol metabolism

  2. Cholesterol • Found in animals • 2gm/kg body weight • Amphipathic in nature

  3. Functions of cholesterol • Structural component of cell membrane • Precursor of steroid hormones • Structural part of lipoproteins • Fatty acids are transported to liver as cholesteryl esters

  4. Input Vs output of cholesterol Dietary cholesterol (500mg/day) Cholesterol by synthesis (500mg/day) Cholesterol pool (1000mg/day) Bile salts and bile acids (250mg/day) Cholesterol lost in bile (500mg/day) Lipoproteins (variable)

  5. Cholesterol biosynthesis • About 1gm/day synthesized • Occur in almost of the tissues but mainly in liver, intestine, adrenal gland and reproductive tissues • Biosynthesis takes place in the cytosol of the cell • Acetyl CoA provides carbon and NADPH reducing equivalents

  6. Biosynthesis has 5 steps • Synthesis of HMG CoA (3C) • Formation of mevalonate (6C) • Production of isoprenoid units (5C) • Synthesis of squalene (30C) • Conversion of squalene to cholesterol (27C)

  7. Regulation of cholesterol biosynthesis • HMG CoA reductase is the rate limiting enzyme • Regulated by: • Feedback control by cholesterol itself • Hormonal regulation: insulin & glucagon • Inhibition by drugs: lovastatin, pravastatin etc

  8. Regulation of HMG CoA (Compactin, Lovastatin) Glucagon Cholesterol -HMG CoA HMG CoA reductase +Mevalonate Insulin, thyroxine

  9. Degradation of cholesterol • Steroid nucleus cannot be degraded to CO2 and H2O • Converted to bile acids • Serve as the precursor for steroid hormones, vitamin D, coprostanol, cholestanol etc. • Excreted in stool

  10. Use of cholesterol • Synthesis of bile acids: • Synthesis of steroid hormones from cholesterol: glucocorticoids, mineralocorticoids, progestins, androgens, estrogens • Synthesis of vitamin D:

  11. Types of cholesterol lipoproteins • Total cholesterol: <200mg/dl • LDL cholesterol: 50-100mg/dl • HDL cholesterol: >40mg/dl • VLDL cholesterol: <50 mg/dl

  12. Calculation • Total cholesterol = LDL chol + HDL chol + VLDL chol • VLDL chol = TAG/5 (for less than 400mg/dl TAG) • So, TC = LDL + HDL + (TAG/5) • Calculated LDL = TC – HDL – TAG/5

  13. Hypercholesterolemia • Increase in plasma total cholesterol (>250mg/dl) • Observed in many disorders • Diabetes mellitus • Hypothyroidism • Obstructive jaundice • Nephrotic syndrome

  14. Control of hypercholesterolemia • Can be controlled by: • Consumption of PUFA • Dietary fiber • Avoiding high carbohydrate diet • Use of drugs

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