Lipoprotein Metabolism Lecture Notes

Introduction to Lipoprotein Metabolism

• Two pathways:
  • Exogenous Pathway: Transport of cholesterol and triglycerides from dietary intake.
  • Endogenous Pathway: Synthesis and transport of cholesterol and lipids within the body.

Exogenous Pathway

Digestion and Transport

1. Intestinal Processing:
   • Triglycerides and cholesterol digested in the small intestine.
   • Bile, containing bile salts, phospholipids, cholesterol, and bilirubin, is secreted by the gallbladder to emulsify fats.
   • Emulsification: breakdown of fat globules into smaller droplets by bile salts, aiding in fat digestion.
2. Enzymatic Breakdown:
   • Pancreatic lipase and co-lipase break down triglycerides into monoglycerides and free fatty acids.
   • Formation of micelles (emulsification droplets with bile salts) that transport lipids to enterocytes.
3. Enterocyte Absorption:
   • Monoglycerides and fatty acids absorbed into enterocytes.
   • Resynthesized into triglycerides in the smooth ER.
   • Apo B48 protein synthesized in the rough ER.
   • Formation of chylomicrons, containing triglycerides, cholesterol, phospholipids, and Apo B48.
   • Chylomicrons enter lymphatic system via lacteals, then blood circulation.

Chylomicrons in Blood Circulation

• HDL donates Apo E and Apo C2 to chylomicrons.
• Lipoprotein Lipase (LPL) Activation:
  • Activated by Apo C2, LPL hydrolyzes triglycerides in chylomicrons.
  • Free fatty acids released, absorbed by muscle and adipose tissue.
  • Chylomicron remnants taken up by liver via Apo E and LDL receptors.

Endogenous Pathway

VLDL Formation and Metabolism

1. VLDL Synthesis:
   • Synthesized in liver with triglycerides, cholesterol, Apo B100.
   • HDL donates Apo E and Apo C2 to VLDL.
2. LPL Activation and IDL Formation:
   • LPL hydrolyzes VLDL triglycerides, forming IDL.
   • IDL can return to liver or be further metabolized by hepatic triglyceride lipase to LDL.

LDL Metabolism

• LDL contains high cholesterol content, delivers cholesterol to tissues.
• Can be oxidized, contributing to atherosclerosis.
• LDL returns to liver or peripheral tissues, including gonads and adrenal cortex, for hormone synthesis.

HDL Metabolism

• Formed from Apo A1, picks up cholesterol from tissues via scavenger receptors (ABCA1, ABCG1).
• Transfers cholesterol to liver (reverse cholesterol transport) or to other lipoproteins (VLDL, IDL, LDL) via cholesterol ester transfer protein (CETP).

Clinical Relevance

• Cholesterol Levels:
  • Total cholesterol should be <200 mg/dL.
  • HDL levels: Males 40-50 mg/dL, Females 50-60 mg/dL.
  • LDL levels: <100 mg/dL preferred.

Summary

• Understanding the pathways of lipoprotein metabolism is crucial for managing lipid disorders and reducing cardiovascular risk.

---

Note: The understanding of lipoprotein metabolism mechanisms is essential for understanding lipid transport and potential implications in cardiovascular health. Be sure to review the role of each lipoprotein and the clinical implications of their levels.