Understanding Lipoprotein Metabolism

Sep 6, 2024

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.