Lecture Notes: Lipoprotein Metabolism

Overview

• Lipoprotein metabolism consists of two pathways:
  • Exogenous Pathway: Transports dietary cholesterol and triglycerides to tissues.
  • Endogenous Pathway: Transports cholesterol and lipids synthesized in the body.

Exogenous Pathway

• Focus on the small intestine where dietary lipids are processed:
  • Triglycerides and cholesterol (free and esters) are present.
  • Chemoreceptors in the enteric system detect fats and stimulate enteroendocrine cells to release cholecystokinin (CCK).
  • CCK affects the gallbladder, leading to bile release.

Bile and Emulsification

• Bile contains:
  • Cholesterol, phospholipids, water, electrolytes
  • Bilirubin (pigment) and bile salts (e.g., colic acid, deoxycolic acid)
• Bile salts emulsify fats, breaking down large fat globules into smaller droplets.
  • This process enhances the effectiveness of pancreatic lipase in breaking down triglycerides into free fatty acids and monoglycerides.

Lipid Absorption

• Bile salts surround and stabilize lipid droplets, forming micelles (500x smaller than emulsion droplets).
• Micelles transport fats towards enterocytes where absorption occurs.
• Inside enterocytes:
  • Free fatty acids and monoglycerides are reassembled into triglycerides within the smooth endoplasmic reticulum.
  • Triglycerides are combined with ApoB48 protein and phospholipids to form chylomicrons.

Chylomicrons

• Transport in lymphatic system via lacteals.
• Enter bloodstream and acquire additional proteins from HDL:
  • ApoE and ApoC2 are added.
  • ApoC2 activates lipoprotein lipase (LPL) in capillaries, releasing free fatty acids and glycerol.
  • Free fatty acids are used for energy in muscles or stored in adipocytes.

Chylomicron Remnants

• After unloading triglycerides, chylomicrons become remnants.
• Remnants are absorbed by the liver via LDL receptors (and other receptors like LRP).
• Cholesterol from remnants can be:
  • Converted into bile salts, stored as cholesterol esters, or incorporated into cell membranes.

Endogenous Pathway

• Liver synthesizes VLDL from triglycerides and cholesterol.
• VLDL also acquires ApoE and ApoC2 from HDL.
• VLDL delivers triglycerides to tissues, becoming IDL (intermediate density lipoprotein) and then LDL (low density lipoprotein).

VLDL Remnants (IDL)

• Can be returned to liver or converted to LDL.
• Involves hepatic triglyceride lipase reducing triglyceride content.
• LDL predominantly carries cholesterol to tissues.

LDL and Atherogenesis

• LDL is known as "bad cholesterol" due to its role in atherosclerosis.
• Can be oxidized, leading to uptake by macrophages and foam cell formation, contributing to plaque development.

HDL: The "Good Cholesterol"

• HDL (high-density lipoprotein) helps remove cholesterol from tissues and transports it back to the liver.
• Functions via scavenger receptors and donates ApoE and ApoC2 to other lipoproteins.
• Aids in cholesterol ester transfer and converts cholesterol to cholesterol esters for storage.

Summary of Lipoproteins and Their Components

• Chylomicrons: Mainly carry triglycerides, about 1% protein.
• VLDL: About 10% protein, carry triglycerides and cholesterol.
• IDL and LDL: Intermediate and low-density, carry more cholesterol.
• HDL: Highest protein (20%), aids in reducing cholesterol.

Blood Cholesterol Levels

• Total cholesterol should be <200 mg/dL.
• HDL: Higher levels are better (40-60 mg/dL for males and females respectively).
• LDL: Lower levels are preferred (<100 mg/dL).

Conclusion

• Understanding lipoprotein metabolism is crucial for managing cardiovascular health.
• Regular lipid panels can help monitor and manage cholesterol levels effectively.