Metabolism 9 Flashcards
What are lipoproteins?
Used for transporting lipids in plasma. Composed of apolipoproteins and lipids
Rank the following in terms of % protein composition (greatest to least):
HDL, LDL, VLDLs, IDLs, chylomicrons
HDL > LDL >IDL > VLDL > chylomicrons
Rank the following in terms of % lipid composition (greatest to least):
HDL, LDL, VLDLs, IDLs, chylomicrons
Chylomicrons > VLDL >IDL >LDL > HDL
What is the general structure of plasma lipoproteins?
Amphipathic Phospholipid micelle with cholesterol embedded and apoproteins
Core made of TAGs, Cholesterol Esters and nonpolar lipids
What is the function of chylomicrons?
Transport dietary TAG from intestines to adipose tissue and other tissues.
What is the main lipid of chylomicron and its apoprotein?
TAG
B-48 (A,C,E)
What is the function of chylomicron remnant?
Deliver remaining dietary TAG to liver. Exchanges TAG for cholesterol ester from HDL and transfers it to liver as well
What lipid and apoprotein make up the chylomicron remnant?
TAG
B-48 (A,C,E)
What lipid and apoprotein make up the VLDL? Where is it formed?
Lipid: TAG
Apoprotein: B-100 (C,E)
Formed in liver
What lipid and apoprotein make up IDL? Where is it formed?
Lipid: TAG and cholesterol
Apoprotein: B-100 (C,E)
Formed via processing of VLDL in circulation (VLDL remnant)
What lipid and apoprotein make up LDL? Where is it formed?
Lipid: Cholesterol
Apoprotein: B-100
Formed via processing of IDL in circulation
What is the function of VLDL?
Transport endogenously synthesized TAG to adipose tissue and heart/skelteal muscle
Exchanges TAG for CE from HDL
What is the function of IDL?
Deliver remaining TAG and cholesterol to the liver
Exchanges TAG for CE from HDL and delievers it to liver
What is the function of LDL?
Deliver cholesterol to the liver and other cells (steroidgenic cells etc)
What is considered “bad cholesterol”?
LDL
What is considered “good cholesterol”?
HDL
What lipid and apoprotein make up HDL? Where is it formed?
Lipid: cholesterol
Apoprotein: A, C, E
Formed in the liver and intestines
What is the function of HDL?
Accepts cholesterol from peripheral cells -> esterifies it -> transports CEs to liver
Exchange CE for TAG in VLDL, IDL, and chylomicron remnants
Atheroprotective via enzymes (Paroxonase) to protect cells against oxidative damage and inhibit LDL oxidation
Resevoir for circulating apoproteins A, C, and E that can be transported to other apoproteins
Chylomicrons transport what kind of lipids?
Dietary exogenous lipids
VLDL, IDL, LDL transport what kind of lipids?
Synthesized endogenous lipids
What function does the apoprotein B-48 serve? What lipoprotein is it found in?
Found in chylomicrons
Function: Chylomicron secretion
What function does the apoprotein B-100 serve? What lipoprotein is it found in?
Found in: VLDL, IDL, LDL
Function: Bind LDL receptor and VLDL secretion
What function does the apoprotein A-1 serve? What lipoprotein is it found in?
Found in HDL
Function: Activates LCAT (for cholesterol esterificatio), Binds HDL receptors
What function does the apoprotein C-II serve? What lipoprotein is it found in?
Found in Chylomicron, VLDL, IDL, HDL
Function: Cofactor for activating lipoprotein lipase
What function does the apoprotein E serve? What lipoprotein is it found in?
Found in chylomicrons, VLDL, IDL, HDL
Function: Clearance by binding to LRP (LDL Receptor Related protein)
Which apoproteins can act as cofactor for enzymes?
Apo-CII: lipoprotein lipase
Apo-A-1: LCAT
Which apoproteins can act as a ligand for EC functional receptor?
Apo E: remnant receptor
Apo B-100: LDL receptor
Apo A-1: HDL receptor
Which apoproteins can act as structural proteins for lipoproteins?
B-48: chylomicrons
B-100: VLDL and LDL
A-1: HDL
What is the sequence for chylomicron?
Dietary TAGs and cholesterol from intestines -> lymph -> Nascet chylomicron (B-48) -> Pick up Apo-CII and Apo-E from HDL (Chylomicron now) -> Lipoprotein Lipase converts TAG to FFA and glycerol -> Chylomicron remnant -> removed by liver via receptor-mediated endocytosis( Apo E binds LDL receptor and LRP)
What is LRP?
LDL receptor related protein
What is the sequence for VLDL?
VLDL transports endogenous TAGs and cholesterol -> picks up Apo E and Apo C-II from hDL -> Lipoprotein Lipase converts TAGs to FFA and glycerol -> VLDL loses TAG and shrinks -> Converted to IDL -> Transfer Apo C-II and Apo E to HDL -> Converted to LDL -> LDL removed from circulation by Apo B-100 binding to LDL receptor in peripheral tissues/macrophages
What happens to any remaining IDL during VLDL transport?
removed from circulation via receptor-mediated endocytosis using LDL receptor binding to Apo B-100 and Apo E and LRP binding to Apo E
What effect does statin have on LDL metabolism?
Inhibits HMC-CoA reductase which is used to synthesize cholesterol
Decreases cholesterol levels
Increases LDL receptors and thus removal of cholesterol from circulation
What are the 2 paths that LDL can take?
LDL receptor mediated uptake
Receptor Independent Uptake
When does the receptor-independent uptake of LDL play an important role?
When LDL cholesterol levels are high
What happens when cholesterol levels are high?
high affinity LDL receptors are downregulated -> decresaes LDL receptor mediated uptake of cholesterol
Does NOT affect receptor-independent uptake
What can happen when LDL cholesterol becomes oxidized?
Oxidized LDL can be taken up by macrophages, which convert them into foam cells that release cytokines promoting smooth muscle cell proliferation and calcification of plaque
What can continued uptake of oxidized LDL lead to?
Coronary Artery disease and atherosclerosis
What role does HDL play in the overall transport of cholesterol?
Involved in REVERSE cholesterol transport
Explain the sequence of HDL transport?
Liver synthesizes discoidal Nascent HDL with Apo A-1, C-II, and E -> HDL takes up cholesterol from peripheral tissues and other lipoproteins -> converts to spherical shape -> ABCA-1 transfers cholesterol to plasma membrane of HDL -> HDL3-> more free cholesterol incorporated -> HDL2 Mature HDL -> esterifies cholesterol with LCAT -> delivers cholesterol to liver for excretion
What role does the enzyme PCAT play?
Enzyme found in HDL that esterifies the cholesterol that is taken up. It is activated by Apo A-1.
Also called LCAT
What are the 2 mechanisms by which mature HDL delivers cholesterol to the liver?
CETP
Receptor mediated Endocytosis
How does CETP work to deliver cholesterol to liver?
mediates transfer of cholesterol esters from HDL to VLDL, IDL, and chylomicron remnants in exchange for TAG (Results in larger HDL2)
The cholesterol rich IDL and chylomicron remnants are then take up by the liver via Apo E binding to LDL receptor and LRP
How are spherical HDLs taken up by the liver via receptor mediated endocytosis?
Apo AI dependent binding to SR-BI (Scavenger receptor protein BI)
What happens to cholesterol that is delivered to the liver?
Converted to bile acids
Repackaged into lipoproteins
How does HDL exert its atheroprotective effects?
Enzymes (Paroxonase) that inhibit LDL oxidaiton in blood vessel intima
Increases NO synthesis by endothelial cells
What does the cholesterol level represent?
HDL + LDL + 20% of triglyceride evel
What are the optimal levels of total cholesterol, HDL, LDL, triglyceride?
Total Cholesterol: 60mg/dl
LDL: <100mg/dl
What is the optimal total/HDL ratio?
3.3:1
What makes up the majority of the lipid composition in HDL, lDL, IDL, VLDL, and chylomicrons?
HDL: unsaturated cholesterol (12%) LDL: Unsaturated cholesterol (35-40%) IDL: Triglycerides (30%) VLDL: Triglycerides (50-65%) Chylomicrons: Triglycerides (84-89%)
