Lipoprotein Metabolism

Overview

• Lipoprotein metabolism involves transporting cholesterol, triglycerides, and other lipids to tissues.
• Two primary pathways:
  • Exogenous Pathway: Lipids from diet.
  • Endogenous Pathway: Lipids synthesized in the body.

Exogenous Pathway

• Begins in the small intestine:
  • Digested lipids (triglycerides, cholesterol, free cholesterol, cholesterol esters) enter the small intestine.
  • Chemo receptors in the enteric nervous system detect fats and stimulate enteroendocrine cells.
• Cholecystokinin (CCK) is released, stimulating the gallbladder to contract and release bile into the small intestine via the bile duct.
  • Bile contains cholesterol, phospholipids, water, electrolytes, bilirubin, and bile salts (e.g., cholic acid, deoxycholic acid).
  • Bile salts perform emulsification, breaking large fat globules into small droplets.

Emulsification Process

• Bile salts have hydrophobic and hydrophilic ends, bind to lipids and water, creating emulsion droplets.
• Pancreatic lipase (with the help of co-lipase) breaks triglycerides into monoglycerides and free fatty acids.
• Micelles form: small droplets containing monoglycerides, free fatty acids, cholesterol, and fat-soluble vitamins (A, D, E, K).
• Micelles move to the enterocyte, where bile salts are recycled, and lipids are absorbed and reassembled into triglycerides.

Formation of Chylomicrons

• Smooth ER: Reassembles monoglycerides and fatty acids into triglycerides.
• Rough ER: Synthesizes Apo-protein B48.
• Components: Triglycerides, cholesterol, cholesterol esters, phospholipids, and Apo-protein B48.
• Lacteals: Chylomicrons are absorbed into lymphatic circulation, eventually entering the bloodstream.

Role of HDL in Chylomicrons

• HDL transfers ApoE and ApoC2 to chylomicrons.
• ApoC2 activates lipoprotein lipase (LPL) in capillaries (muscle and adipose tissue).
• LPL breaks down triglycerides into free fatty acids and glycerol:
  • Free fatty acids are used for energy in muscle or stored in adipose tissue.
  • Glycerol is used in the liver.
• Chylomicron remnants (with ApoB48 and ApoE) return to the liver.

Endogenous Pathway

• Liver synthesizes VLDL containing triglycerides, cholesterol, phospholipids, and ApoB100.
• HDL provides ApoE and ApoC2 to VLDL.
• LPL acts on VLDL, creating free fatty acids and glycerol.
• VLDL remnants (IDL) can return to the liver or be converted to LDL through further triglyceride depletion by hepatic triglyceride lipase.

LDL Function

• LDL distributes cholesterol to peripheral tissues and organs (e.g., adrenal cortex, gonads) for hormone synthesis.
• LDL receptors in various tissues facilitate uptake.
• In the blood, LDL can become oxidized and taken up by macrophages, contributing to atherosclerosis.

HDL Function

• HDL starts as ApoA1, becoming nascent HDL then mature HDL through cholesterol uptake from cells.
• HDL can deliver cholesterol to steroidogenic tissues (adrenal cortex, gonads) via scavenger receptors (SR-B1).
• HDL helps in reverse cholesterol transport, moving cholesterol from tissues to the liver for excretion or recycling.

Lipoprotein Composition

• Chylomicrons: 1% protein, 90% triglyceride.
• VLDL: 10% protein, 55% triglyceride.
• IDL: 10% protein, 30% triglyceride, 35% cholesterol esters.
• LDL: 20% protein, 15% triglyceride, 50% cholesterol esters.
• HDL: 50% protein, 15% triglyceride, 30% cholesterol esters.

Lipid Profile

• Total serum cholesterol: <200 mg/dL preferred.
• HDL levels:
  • Males: 40-50 mg/dL
  • Females: 50-60 mg/dL (higher is better)
• LDL levels: <100 mg/dL (lower is better, <129 mg/dL acceptable but borderline).

Key Notes

• Apolipoproteins: Essential for lipoprotein structure and function (e.g., ApoB48, ApoB100, ApoE, ApoC2, ApoA1).
• Enzymes: Lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL), and cholesterol ester transfer protein (CETP) are crucial in lipid metabolism.
• Lipoproteins and Disease: Imbalance can lead to conditions like atherosclerosis, due in part to oxidized or glycated LDL.

Remember: HDL is "good" cholesterol helping transport lipids back to the liver, whereas LDL is "bad" cholesterol associated with plaque formation in arteries.