Lipoprotein Metabolism Lecture Notes

Overview

• Discussing lipoprotein metabolism involving two primary pathways:
  • Exogenous Pathway: Transport of lipids (cholesterol, triglycerides) from diet to tissues.
  • Endogenous Pathway: Transport of lipids synthesized in the body to various tissues.

Exogenous Pathway

Digestion and Transport

• Digestion in the Small Intestine:
  • Ingested triglycerides and cholesterol are processed.
  • Chemoreceptors in the mucosa detect lipids, stimulating the release of Cholecystokinin (CCK).
  • CCK stimulates the gallbladder to release bile.

Bile Composition

• Bile Components:
  • Water, cholesterol, phospholipids, electrolytes, bilirubin, and bile salts (e.g., colic acid, deoxycholic acid).
• Function of Bile Salts:
  • Emulsification of fats, breaking large fat globules into smaller droplets for enzyme action.

Pancreatic Lipase Action

• Pancreatic Lipase:
  • Acts on emulsified fats to break triglycerides into:
    • Monoglycerides
    • Free Fatty Acids
• Micelle Formation:
  • Monoglycerides, fatty acids, cholesterol, and fat-soluble vitamins (A, D, E, K) form micelles, facilitating absorption into enterocytes.

Enterocyte Processing

• Monoglycerides and fatty acids are absorbed and transported to the Smooth Endoplasmic Reticulum.
• Triglycerides are resynthesized and packaged with ApoB48 protein and phospholipids into Chylomicrons.

Chylomicron and Circulation

• Chylomicrons enter lymphatic circulation (lacteals) then into the blood via the thoracic duct.
• Chylomicrons deliver triglycerides to:
  • Skeletal and cardiac muscles (energy use).
  • Adipose tissue (storage).

Lipoprotein Lipase Action

• ApoC2 on chylomicrons activates Lipoprotein Lipase (LPL).
• LPL breaks down triglycerides into free fatty acids and glycerol for uptake by tissues.
• After triglyceride hydrolysis, chylomicrons become Chylomicron Remnants, which return to the liver.

Endogenous Pathway

VLDL Formation

• VLDL (Very Low-Density Lipoprotein) is formed in the liver from:
  • Triglycerides and cholesterol (from chylomicrons or synthesized from glucose).
• VLDL is also modified by HDL, receiving ApoE and ApoC2.

VLDL Function

• VLDL delivers triglycerides to peripheral tissues (muscles, adipose tissue) via LPL.
• After triglyceride loss, VLDL becomes IDL (Intermediate Density Lipoprotein), which can return to the liver or undergo further conversion.

IDL and LDL Formation

• IDL can:
  • Be converted to LDL (Low-Density Lipoprotein) which predominantly carries cholesterol.
  • Interact with receptors in the liver and adrenal cortex.
• LDL delivers cholesterol to tissues (gonads, adrenal cortex) and eventually returns to the liver for recycling.

Atherogenic Risks

• Prolonged exposure of LDL in blood can lead to oxidation, forming Oxidized LDL.
• Oxidized LDL is taken up by macrophages, leading to Foam Cell formation and potential atherosclerosis.

HDL Role

• HDL (High-Density Lipoprotein) is protective against atherosclerosis:
  • Binds excess cholesterol from foam cells.
  • Transfers cholesterol to steroidogenic tissues and LDL.

Lipoprotein Composition Summary

• Percentages of protein, triglycerides, cholesterol, and cholesterol esters in lipoproteins:
  • Chylomicrons: 1% protein, ~90% triglycerides
  • VLDL: 10% protein, ~55% triglycerides
  • IDL: 10% protein, ~30% triglycerides
  • LDL: 20% protein, ~15% triglycerides
  • HDL: ~50% protein, ~15% triglycerides

Serum Cholesterol Levels

• Total Serum Cholesterol: < 200 mg/dL is ideal.
• HDL Levels:
  • Males: 40-50 mg/dL
  • Females: 50-60 mg/dL
• LDL Levels: Ideally < 100 mg/dL, < 129 mg/dL is borderline.

Conclusion

• Understanding lipoprotein metabolism is critical for identifying risks related to cardiovascular diseases.