Figure: lipoprotein metabolism
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Introduction
VLDL
- VLDL* is synthesized & secreted by hepatocytes.
- VLDL synthesis is stimulated by caloric intake without regard to caloric source.
- IDL* & LDL* are derived from VLDL through the action of tissue lipoprotein lipase.
- the VLDL particles transport hepatic-derived cholesterol & triglycerides to peripheral tissues.
- apo C2 is a cofactor of tissue lipoprotein lipase which removes most of the triglycerides from VLDL
- as VLDL is metabolized, apo C2 & apo C3 are transferred to HDL*.
IDL
- IDL is formed from VLDL.
- it is a short-lived particle containing approximately equal amounts of triglyceride & cholesterol & apo B100 & apo E
LDL
- the mature LDL particle is formed from IDL by the continued action of lipoprotein lipase
- apo E-mediated hepatic lipase activity may also participate in formation of the mature LDL particle (alternate pathway)
- LDL catabolism takes place in the liver & the periphery by receptor-mediated endocytosis.
HDL3
- both the liver & the intestine are involved in production of HDL
- HDL is produced as a discoid-shaped particle containing apo A1, +/- apo A2, lecithin & cholesterol (nascent HDL)
- LCAT* activity is necessary for transformation of this nascent HDL into HDL3, a spherical lipid-transporting moiety containing apo A1, apo A2, apo C1, apo C2, apo C3, apo D & apo E
- apo A1 stimulates LCAT activity
- apo A2 may associate with esterfied cholesterol & facilitate entry of esterfied cholesterol into the core of the HDL particle
- apo A2 inhibits LCAT activity
- thus is formed HDL3
HDL2
- formation of HDL2 from HDL3 occurs in tissues in association with VLDL & chylomicron metabolism
- thus conversion of HDL3 to HDL2 results in an uptake of cholesterol & triglyceride
- HDL3 may be regenerated from HDL2 by the action of hepatic lipase
- thus HDL facilitates return of cholesterol & triglycerides from the periphery to the liver (reverse cholesterol transport)
- HDL2 metabolism presumably occurs in peripheral tissues (liver, kidney, muscle etc)
chylomicrons
- chylomicrons are synthesized & secreted by intestinal epithelium into the lymphatics
- triglyceride constitutes more than 80% of the chylomicron particle by weight
- apo-B48, apo A1, apo A2, apo A4 collectively constitute < 2% of chylomicrons by weight
- during traversal of the lymphatics enroute to entry of the venous circulation through the thoracic duct, chylomicrons accumulate apo C from HDL filtered into the lymph from the plasma
- after entry into the systemic circulation, chylomicrons are metabolized in tissues through the action of lipoprotein lipase
chylomicron remnant
- the remaining chylomicron remnant containing apolipoproteins B48 & E are rapidly removed by the low-density lipoprotein related protein (LRP or chylomicron-remnant receptor) in the liver
- the chylomicron remnants are removed by receptor-mediated endocytosis & degraded in hepatic lysosomes
* LCAT = lecithin cholesterol acyltransferase
* VLDL = very low density lipoprotein
* IDL = intermediate density lipoprotein
* LDL = high density lipoprotein
* HDL = high density lipoprotein
* apo = apolipoprotein
References
- ↑ Tietz Textbook of Clinical Chemistry, 2nd ed. Burtis CA & Ashwood ER (eds), WB Saunders Co, Philadelphia PA, 1993, pg 1024