Lipoprotein Metabolism Lecture Notes

Overview

• Lipoprotein Metabolism: Process of transporting cholesterol, triglycerides, and lipids to various tissues.
• Two Pathways:
  • Exogenous Pathway: Lipids from diet.
  • Endogenous Pathway: Lipids synthesized in the body.

Exogenous Pathway

• Intestinal Absorption:
  • Lipids from the stomach are pushed into the small intestine.
  • Enteric nervous system detects fats, releasing enteroendocrine hormone cholecystokinin (CCK).
• Bile Production & Function:
  • Gallbladder releases bile into intestines via bile duct.
  • Bile salts (e.g., cholic acid) emulsify fats into smaller droplets (emulsion droplets), making them soluble in intestinal fluid.
• Enzymatic Breakdown:
  • Pancreatic lipase, with co-lipase, breaks triglycerides into monoglycerides and free fatty acids.

Lipid Absorption and Chylomicron Formation

• Micelle Formation:
  • Emulsion droplets further breakdown into micelles (500 times smaller).
  • Micelles contain monoglycerides, free fatty acids, cholesterol, and fat-soluble vitamins (A, D, E, K).
• Intestinal Absorption:
  • Monoglycerides and free fatty acids absorbed into enterocytes, reform triglycerides.
• Formation of Chylomicrons:
  • Triglycerides, cholesterol, and apolipoprotein B48 form chylomicrons.
  • Chylomicrons enter lymphatic system via lacteals, then into bloodstream via thoracic duct.

Chylomicron Metabolism

• Function and Fatty Acid Delivery:
  • Chylomicrons deliver fatty acids to muscles and adipose tissue.
  • Lipoprotein lipase (LPL) in capillaries breaks down triglycerides in chylomicrons.
• Chylomicron Remnants:
  • After triglyceride delivery, remnants return to liver for recycling.

Endogenous Pathway

• VLDL Formation:
  • Liver repackages triglycerides and cholesterol into VLDL (very low-density lipoprotein).
  • VLDL receives Apo E and C2 from HDL.
• VLDL Metabolism:
  • LPL acts on VLDL, releasing fatty acids to tissues.
  • VLDL becomes IDL (intermediate-density lipoprotein) and eventually LDL (low-density lipoprotein).

LDL and Cholesterol Transport

• LDL Function:
  • LDL delivers cholesterol to peripheral tissues and returns to liver.
  • High LDL levels can lead to atherosclerosis due to oxidized LDL uptake by macrophages.

HDL and Reverse Cholesterol Transport

• HDL Function:
  • HDL collects excess cholesterol from tissues and returns it to the liver.
  • Facilitates cholesterol transfer to VLDL, IDL, and LDL via CETP (cholesterol ester transfer protein).

Clinical Considerations

• Lipid Profile Targets:
  • Total Cholesterol: <200 mg/dL
  • HDL: Higher is better; Males 40-50 mg/dL, Females 50-60 mg/dL.
  • LDL: <100 mg/dL preferred.

Conclusion

• Understanding lipoprotein metabolism is crucial for managing cholesterol and preventing atherosclerosis.
• Monitoring lipid profiles helps assess cardiovascular risk.

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Note: These notes aim to provide a high-level overview of lipoprotein metabolism based on the lecture's content. For detailed understanding, refer to original lecture material or additional resources.