L16: Lipoproteins Flashcards
LO1/LO2: Describe the major differences in the composition, physical properties, and apoprotein content of chylomicrons and VLDLs
chylomicrons (transport triglycerides, intestine): largest, lowest density, primarily lipids (mostly TAGs), ApoB-48, ApoC11, Apo E
VLDLs (transport triglycerides, liver): second largest, second lowest density, primarily lipids (majority TAGs, followed by PL, CE, C), ApoB-100, ApoC11, ApoE
LO1/LO2: Describe the major differences in the composition, physical properties, and apoprotein content of LDLs and HDLs
LDLs (transport cholesterol, plasma IDL): second smallest, more dense, 79% lipids/21% proteins, (half CE, remaining PL, TAG, CE), ApoB-100
HDLs (reservoir of apoproteins/reverse cholesterol transport, liver+intestine): smallest, highest density, equal parts protein+lipid (mostly CE and PL with some TAGs and C), Apo A, Apo C, Apo E
LO2: List the functions of the major classes of lipoproteins and where each is formed
CHYLOMICRONS-transport dietary triglycerides to peripheral tissues; formed in intestine
VLDLs- transport triglycerides to peripheral tissues; formed in liver
IDLs- transport triglycerides/precursors to LDLs; formed in plasma VLDL
LDLs- transport cholesterol to peripheral tissues; formed in plasma IDL
HDLs- reservoir of apoproteins/reverse cholesterol transport; formed in liver+intestine
LO3: Name two apoproteins that serve as ligands for cell surface receptors and two apoproteins that are activators of enzymes involved in lipoprotein metabolism
LIGANDS FOR RECEPTORS
Apo E: recognition of remnant receptors to initiate receptor-mediated endocytosis in liver
Apo B-100: recognition of LDL receptors to initiate receptor-mediated endocytosis
ACTIVATORS OF ENZYMES
Apo A-1: stimulates LCAT to esterify cholesterol for mobilization for reverse cholesterol transport
Apo CII: triggers LPL to hydrolyze triglycerides from chylomicrons into blood stream
LO4: Describe the function, location, and regulation of LPL
FUNCTION
-hydrolyze the triglycerides in circulating chylomicrons to free fatty acids and glycerol
LOCATION
-bound by heparin sulfate in the luminal wall of capillaries in most tissues (enriched in the capillary bed of adipose, muscle, and cardiac tissue)
REGULATION
- activated by ApoCII
- synthesis in adipocytes stimulated by insulin
- synthesis in other tissues not affected by insulin
LO5: Compare/contrast the properties of LPL and hepatic lipase
HEPATIC LIPASE
FUNCTION
-metabolizes 25% of IDLs to LDLs (remaining LDLS bind to remnant receptors (via apo E) or LDL receptors (via apo B)
-can break apart phospholipids
LOCATION
-sinusoidal surfaces of liver only
REGULATION
-also activated by ApoCII
LO6: Describe the steps involved in the reverse transport of cholesterol (4)
NET TRANSFER OF CHOLESTEROL FROM TISSUES TO LIVER FOR PROCESSING FOR EXCRETION
- Cholesterol is removed from peripheral tissues by HDL (requires ApoA-1)
- rate controlling step; mediated by ATP-binding cassette transporter (ABCA1) - Cholesterol can then be esterified by LCAT (in plasma)
- stimulated by Apo A-1
- then transferred to core of HDL particle or to other lipoprotein remnants - Esters transferred from HDL to lipoprotein remnants, in space created by lipoprotein lipase-catalyzed hydrolysis of triglycerides (mediated by Apo D)
- HDL cholesterol esters then transferred to tissues via scavenger receptor B1, which takes up esters but not HDL
- B1 expressed on liver, adrenals, testes, ovaries, and macrophages in atherosclerotic plaques
Steps 3+4 regenerates lipid-poor HDL, which can reinitiate the cycle at Step 1.
LO7: Compare/contrast LDL receptors and remnant receptors with respect to their location and function in lipid metabolism
LDL RECEPTORS
- bind ApoB-100 protein
- on liver cells
- assist with LDL and ILDL uptake and recycling
- less localized/more prolific (found in peripheral tissues also)
- synthesis regulated by [cholesterol]
REMNANT RECEPTORS
- bind Apo E protein
- on liver cells
- assist with LDL and ILDL uptake and recycling
LO8: Describe two metabolic fates of IDLs
-either taken up by liver, or further metabolized by hepatic lipase to LDLs (lose ApoCII and ApoE)
LO9: Compare/contrast the properties of LDL receptors and scavenger receptors
LDL RECEPTORS
- bind ApoB-100 protein
- on liver cells
- assist with LDL (75%) and ILDL uptake and recycling
- less localized/more prolific (found in peripheral tissues also)
- synthesis regulated by [cholesterol]
SCAVENGER RECEPTORS
- removes 25% of plasma LDLs
- located on macrophages
- synthesis not regulated by [cholesterol]
LO10: Describe the metabolic role of the ABCA1 protein and name the disorder that results from a defect or deficiency in this protein
-assists with transfer of unesterified cholesterol/phospholipids from peripheral cells to nascent HDL (rate-limiting step of reverse cholesterol transport)
TANGIER’S DISEASE
- deficiency in HDL secondary to deficiency in ABCA1 protein
- results in low Apo A1 levels (1-3% of normal)
- decreased cholesterol and increased triglycerides
- diagnosed in early childhood, as tonsils become enlarged/yellow orange as they fill with foam cells
LO11: Describe the molecular defect underlying familial hypercholesterolemia
TYPE II HYPERLIPOPROTEINEMIA
- inherited defect in LDL receptor, so LDLs can’t be taken up from the blood
- most common disease in lipid metabolism
- carriers have increased risk of atherosclerotic plaques/disease (autosomal dominant)
- homozygotes have very severe disease
