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
- Lipoprotein lipase (LPL), bound to the endothelial layer of peripheral capillaries.
- 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
