Chylomicron Metabolism

LIPOPROTEIN METABOLISM

  • Exogenous pathway: chylomicrons clear dietary lipids
  • Endogenous pathway: VLDL and LDL transport/distribute endogenously synthesized lipids
  • Reverse cholesterol transport: HDL clears excess plasma cholesterol

Enzymes

  • Degrade triacylglycerol to glycerol and free fatty acids
  1. Lipoprotein lipase (LPL), bound to the endothelial layer of peripheral capillaries.
  2. Hepatic lipase, localizes within hepatic endothelial cells.

CHYLOMICRONS

  • Fed state only
  • Cleared ~ minutes
  • 98% lipids (1.TAG 2. Free/esterified cholesterol)
  • ApoB-48 = dietary lipoprotein marker

EXOGENOUS PATHWAY

  • Only occurs in the fed state.
  • Clears dietary lipids
    Step 1: Dietary lipids are packaged into a chylomicron
    Step 2: Chylomicron enters lymphatic system (empties into circulation via left subclavian vein)
    Step 3: HDL donates ApoE and ApoC-II to chylomicron
    Step 4: ApoC-II binds/activates LPL (peripheral tissues)
    Step 5: LPL degrades TAG into glycerol & FFA
  • FA enter tissues & glycerol returns to liver
  • Chylomicron = chylomicron remnant (low TAG, high CE and C)
    Step 6: ApoC-II returns to HDL
    Step 7: Apo E binds liver remnant receptor: chylomicron endocytosis
    Step 8: Remnant releases cholesterol in liver
  • Remnant degraded by lysosomes

CLINICAL CORRELATION

Familial Hyperchylomicronemia

  • Rare hereditary disease
  • LPL or ApoC-II deficiency: cannot clear chylomicrons
  • Fasting blood plasma: cloudy
  • Lipemia retinalis: cloudy appearance of capillaries in the retina

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