Biosynthesis of Cholesterol Notes

Order of the Cholesterol Pathway

  1. Acetyl CoA

  2. HMG-CoA

  3. Mevalonate

  4. Isoprenoid Units (Farnesyl Pyrophosphate)

  5. Squalene

  6. Lanosterol

  7. Cholesterol

How to Inhibit Cholesterol Synthesis

  • Dietary Approaches: Reduce saturated fat intake and include more soluble fiber.

  • Medications: Statins inhibit HMG-CoA reductase, lowering cholesterol synthesis.

Hormones Involved in the Release of Bile

  • Cholecystokinin (CCK): Stimulates the gallbladder to contract and release bile into the intestine.

  • Secretin: Promotes the production of bile from the liver and regulates its release.

Functions of Cholesterol in Metabolism

  • Component of Cell Membranes: Maintains structural integrity and fluidity.

  • Precursor for Important Biomolecules:

  • Bile Acids: Aid in digestion and absorption of dietary fats.

  • Steroid Hormones: Hormones like cortisol, testosterone, and estrogen.

  • Vitamin D: Important for calcium homeostasis and bone health.

Cholesterol Synthesis - Key Intermediates

  1. Acetyl-CoA

  2. HMG-CoA (3-Hydroxy-3-Methyl-Glutaryl-CoA)

  3. Mevalonate

  4. Isoprenoid Units: Converted from Mevalonate to Farnesyl Pyrophosphate

  5. Squalene: Formed from farnesyl pyrophosphate

  6. Lanosterol: Intermediate before conversion to cholesterol

  7. Cholesterol: Final product

Cholesterol End Products

  • Bile Acids: Synthesized from cholesterol for fat digestion.

  • Steroid Hormones: Such as progesterone, cortisol, testosterone, and estradiol.

  • Vitamin D: Derived from cholesterol.

Statin Drugs and Their Mechanism

  • Mechanism: Statin drugs inhibit HMG-CoA reductase, which is a key enzyme in cholesterol synthesis.

  • Examples: Lipitor, Zocor, Provachol

  • Side Effects: May lead to reduced levels of CoQ10; supplementation recommended.

Cholesterol as a Precursor

  • Cholesterol serves as a precursor for:

  • Bile Acids: Include cholic acid and chenodeoxycholic acid.

  • Steroid Hormones: e.g., progesterone to cortisol and testosterone.

  • Vitamin D: Important for bone health.