Lipoprotein Metabolism Lecture Notes

Overview

• Lipoprotein metabolism involves the transportation of lipids (cholesterol, triglycerides) within the body.
• Two pathways:
  • Exogenous Pathway: Transports dietary lipids.
  • Endogenous Pathway: Transports lipids synthesized by the body.

Exogenous Pathway

• Location: Begins in the small intestine.
• Process:
  • Triglycerides and cholesterol are digested in the intestine.
  • Fats enter the small intestine, triggering enteroendocrine cells to release cholecystokinin.
  • Cholecystokinin stimulates the gallbladder to release bile into the intestine.
  • Bile contains cholesterol, phospholipids, electrolytes, bilirubin, and most importantly, bile salts.
  • Bile salts help emulsify large fat globules into smaller droplets for digestion.

Emulsification and Digestion

• Bile Salts: Have hydrophobic and hydrophilic ends for emulsification.
• Pancreatic Lipase: Secreted by the pancreas to break down triglycerides into monoglycerides and free fatty acids.
• Micelle Formation: Small emulsified droplets form micelles containing monoglycerides, free fatty acids, cholesterol, and vitamins.

Absorption and Chylomicron Formation

• Micelles release contents into enterocytes (intestinal cells).
• Smooth ER: Reassembles triglycerides.
• Rough ER: Produces apoprotein B48.
• Chylomicrons: Lipoprotein particles containing triglycerides, cholesterol, and apoprotein B48.
• Transport: Chylomicrons enter the lymphatic system via lacteals and then the bloodstream.

Transport and Metabolism

• Chylomicrons deliver triglycerides to muscles (for energy) and adipose tissue (for storage).
• Lipoprotein Lipase: Activated by apoprotein C2, breaks down triglycerides into free fatty acids and glycerol.
• Chylomicron Remnants: Return to the liver to be repurposed.

Endogenous Pathway

• VLDL Formation: The liver repackages triglycerides and cholesterol with apoprotein B100 into VLDL.
• HDL Interaction: Donates apoproteins and cholesterol to VLDL.
• Lipoprotein Lipase: Again breaks down VLDL triglycerides; VLDL becomes IDL and eventually LDL.

LDL and HDL

• LDL (Low-Density Lipoprotein): Major carrier of cholesterol to tissues, can lead to atherosclerosis if oxidized.
• HDL (High-Density Lipoprotein): Collects cholesterol from tissues and blood vessels, considered "good cholesterol."

Cholesterol Handling

• Liver: Converts cholesterol to bile salts, stores it as cholesterol esters, or integrates it into cell membranes.
• Steroid Hormones: Cholesterol is a precursor for steroid hormones in adrenal cortex and gonads.

Significant Enzymes and Proteins

• Lipoprotein Lipase (LPL): Breaks down triglycerides.
• Hepatic Triglyceride Lipase (HTGL): Further metabolizes IDL to LDL.
• Scavenger Receptors (SR-B1, ABCA1): Involved in cholesterol metabolism and HDL function.

Health Implications

• Cholesterol Levels:
  • Total cholesterol: Preferred < 200 mg/dL.
  • HDL: Higher is better; > 50 mg/dL for women, > 40 mg/dL for men.
  • LDL: Lower is better; < 100 mg/dL is ideal.

Concept Recap

• Lipoproteins: Classified by density, which correlates with protein content.
  • Chylomicrons: Least dense, mostly triglycerides.
  • HDL: Most dense, high protein content.

Conclusion

• Understanding lipoprotein metabolism is crucial for managing cardiovascular health.
• Regulation of lipid levels and lipoprotein functions can prevent atherosclerosis and other lipid-related disorders.