3.2.2. Lipoprotein metabolism Flashcards
What are lipoproteins?
Complexes of lipids (triacylglycerols, phospholipids, cholesterol, fat soluble vitamins) and proteins
What is the role of lipoproteins in the body?
They transport the bulk of the body’s lipids from the sites where they are made, to the sites where they are needed.
What are the three major classes of lipoproteins?
Chylomicrons, VLDL (Very Low Density Lipoproteins) and HDL (High Density Lipoproteins)
What is the exogenous pathway of lipoprotein metabolism?
The transportation of dietary lipids to the periphery and the liver.
What is the endogenous pathway of lipoprotein metabolism?
The transportation of lipids from the liver to the periphery.
Describe the properties of chylomicrons:
- a class of lipoprotein
- synthesized from dietary lipids in the intestinal epithelia, secreted into lymph, and delivered via thoracic duct to systemic circulation
- low density, rich in TG
- deliver fatty acids to muscle for energy and adipose TG storage
- nascent chylomicrons acquire ApoCII and ApoE from HDL to become mature chylomicrons
- chylomicrons associated with ApoB-48 (made in the RER)
Describe the properties of VLDLs:
- VLDLs are synthesized in the liver and transport TGs to extrahepatic tissues
- VLDLs are low density, rich in TG
- TGs are hydrolyzed by LPL (lipoprotein lipase) converting VLDL to IDL. IDL is further metabolized to LDL
- cholesterol-rich LDL is taken up by receptor-mediated endocytosis (macrophages take up oxidized LDL via scavenger receptors, forming foam cells)
- nascent VLDLs acquire ApoCII and ApoE from HDL to become mature VLDLs
- VLDLs associated with ApoB-100 (made in the RER)
Describe the properties and functions of HDL:
- high density, rich in phospholipids and cholesterol
- involved in maturation of nascent chylomicrons and VLDLs (remodeling), i.e. ApoCII and ApoE
- involved in reverse cholesterol transport (retrieves cholesterol from cholesterol-rich cells and returns it to the liver for disposal)
How does atherosclerosis develop?
- LDL invades intimal space of vessel, where it is sequestered from plasma antioxidants
- LDL oxidation products trigger immune response (leukocytes), production of adhesion molecules and scavenger receptors
- Foam cells (phagocytes filled with cholesterol) form a plaque that invades arterial space
What is the pathogenesis of atherosclerosis?
- Endothelial damage (LDL particles prone to pass between endothelial cells)
- induces protective response (production of cellular adhesion molecules)
- endothelial cells further respond by attracting monocyte white blood cells, which penetrate arterial walls and transform to macrophages
- macrophages take up oxidized LDL cholesterol
- lipid-rich foam cells form
- fatty streak and plaque–>can eventually lead to occlusive intraluminal thrombus
What are some defects in LDL uptake (familial hypercholesterolemia)?
- Mutations in LDL receptor
2. Mutations in ApoB-100
What is Tangier disease?
Mutations in ABC1 gene (the cholesterol efflux pump):
- buildup of cholesterol in tonsils and other organs
- enlarged, yellow-orange tonsils
- reduced efflux of cholesterol from peripheral tissues including macrophages (foam cells form–>premature atherosclerosis)
List 3 categories of dyslipidemias:
- Familial Hypercholesterolemia (FH): defective LDL receptors or mutation in ApoB-100
- Hypertriglyceridemia: LPL or apoC-II defects (unable to process chylomicrons and VLDL)
- Tangier disease: mutations in ABC1 (cholesterol efflux pump, low HDL levels, accumulation of cholesterol)
What is ApoE required for?
It is required for receptor-mediated uptake by the liver.
What is ApoCII required for?
It is required for activating lipoprotein lipase (LPL)
