Biosynthesis of Cholesterol

Functions of Cholesterol

• Component of mammalian cell membranes
• Precursor for bile acids, steroid hormones, and Vitamin D

Disorders Related to Cholesterol Metabolism

• Cardiovascular disease
• Gallstones (not visible on X-ray, detected via ultrasound)

Cholesterol Sources in the Body

• 70% synthesized in the body
• 30% obtained from diet (animal sources: eggs, meat, milk)
• Typical Western diet: 500-2000 mg/day

Cholesterol Synthesis Sites

• Main site: Liver
• Other sites: Intestine, adrenal cortex, gonads

Energetic Cost of Cholesterol Production

• Requires: 18 moles of acetyl CoA, ATP, and 16 moles of NADPH

Stages of Cholesterol Synthesis

• 1. Acetyl-CoA -> HMG-CoA -> Mevalonate
• 2. Mevalonate -> Active Isoprenoid Units (farnesyl pyrophosphate)
• 3. Two farnesyl pyrophosphate -> Squalene
• 4. Squalene -> Lanosterol
• 5. Lanosterol -> Cholesterol

Regulation of Cholesterol Synthesis

• HMG-CoA Reductase:
• Allosteric enzyme regulated by glucagon, cortisol (inhibition) and insulin, T3 (activation)
• Factors increasing/free cholesterol include de novo synthesis and dietary intake.
• Factors decreasing/free cholesterol include inhibition of biosynthesis and LDL receptor downregulation.

Drugs Impacting Cholesterol Levels

• Statins inhibit HMG-CoA Reductase
• Examples: Lipitor, Zocor, Provochol (may necessitate CoQ10 supplementation)

Bile Acids

• Synthesized from cholesterol in the liver, primarily cholic and chenodeoxycholic acids
• Important for fat digestion; secreted in a hormone-controlled manner
• Up to 98% of bile acids are reabsorbed in the enterohepatic circulation

Natural Remedies for Lowering Cholesterol

• Vitamin C aids in bile acid synthesis
• Oat bran binds cholesterol and promotes its excretion

Synthesis of Steroid Hormones

• Cholesterol is converted to various steroid hormones including progesterone, cortisol, and testosterone.