Lipoprotein Metabolism Lecture Notes

Introduction to Lipoprotein Metabolism

• Two Main Pathways:
  • Exogenous Pathway: Transports cholesterol and triglycerides from the diet to different tissues.
  • Endogenous Pathway: Involves cholesterol and lipids synthesized within the body, transported to various tissues.

Exogenous Pathway

Small Intestine Involvement

• Digestion of Lipids:
  • Triglycerides and cholesterol are digested in the small intestine.
  • Chemo receptors detect fat, stimulating enteroendocrine cells to release cholecystokinin (CCK).

Role of CCK

• Gallbladder Function: CCK stimulates gallbladder to contract and release bile.
  • Bile Components: Cholesterol, phospholipids, water, electrolytes, bilirubin, and bile salts (e.g., cholic acid, deoxycholic acid).

Emulsification Process

• Bile Salts: Aid in emulsifying fat by breaking down large fat globules into smaller droplets.
  • Hydrophilic and Hydrophobic Ends: Interact with water and lipids, respectively.

Pancreatic Enzymes

• Pancreatic Lipase: Breaks down triglycerides into monoglycerides and free fatty acids, facilitated by colipase.
• Formation of micelles: Smaller, compact structures that include monoglycerides, free fatty acids, cholesterol, and fat-soluble vitamins.

Absorption and Formation of Chylomicrons

• Enterocytes: Absorb micelles, reassemble triglycerides using smooth endoplasmic reticulum.
• Chylomicron Composition: Triglycerides, cholesterol, phospholipids, and apoprotein B48.
• Transport: Chylomicrons enter lymphatic system (lacteals), then into blood via the thoracic duct.

Lipoprotein Classes and Functions

Chylomicrons

• Role: Transport dietary triglycerides and cholesterol to tissues.
• Interaction with HDL: Receives apoC-II and apoE to become fully functional.
• Lipoprotein Lipase Activation: Facilitates release of free fatty acids and glycerol to adipose and muscle tissues.

VLDL (Very Low-Density Lipoprotein)

• Formation: Synthesized in the liver, composed of triglycerides, cholesterol, and apoprotein B100.
• HDL Interaction: Receives apoC-II and apoE from HDL.
• Function: Transports endogenous triglycerides to tissues.

IDL (Intermediate-Density Lipoprotein)

• Formation: VLDL remnant after triglyceride removal.
• Fate: Can be taken up by the liver or converted to LDL.

LDL (Low-Density Lipoprotein)

• Role: Major cholesterol carrier in blood.
• Receptor Interaction: Binds to LDL receptors in liver and peripheral tissues.
• Risks: High levels lead to atherosclerosis due to oxidation and uptake by macrophages forming foam cells.

HDL (High-Density Lipoprotein)

• Function: Removes cholesterol from tissues and foam cells, transporting it back to the liver.
• Scavenger Receptors: ApoA-I binds to ABC transporters, facilitating cholesterol uptake.
• Cholesterol Transfer: Exchanges cholesterol for triglycerides with other lipoproteins via CETP.

Key Takeaways

• Protein and Lipid Composition: Determines density and function of lipoproteins.
• Health Metrics:
  • Total serum cholesterol should be less than 200 mg/dL.
  • HDL: Higher levels are better (40-60 mg/dL depending on gender).
  • LDL: Lower levels are better, ideally less than 100 mg/dL.

Conclusion

• Importance of understanding lipoprotein metabolism for cardiovascular health.
• Encouragement to review additional resources for deeper understanding.

Additional Recommendations

• Review specific roles of enzymes and apoproteins in lipoprotein metabolism.
• Understand the impact of diet and lifestyle on cholesterol and triglyceride levels.