Metabolism: Lipoproteins Flashcards
Which lipoprotein has the highest protein:lipid ratio? the lowest?
high = HDL low = chylomicron
Describe the structure of a lipoprotein.
core = TAG and cholesterol esters
membrane = phospholipids and free cholesterol
peripheral apoproteins = exchangeable
integral apoproteins = indicative of lipoprotein type
Where are lipoproteins made? What is the difference between these kinds?
liver = endogenous synthesis of TAG, cholesterol intestines = dietary
What is the density of the lipoproteins referring to?
density of proteins
HDL = high protein content
hence, HDL is more negative
Compare the structures of chylomicrons, VLDL, LDL, and HDL.
chylomicrons - largest; lots of TAG
VLDL - next largest; next amount of TAG
LDL - smaller; increase concentration of cholesterol esters:TAG
HDL - smallest; mostly cholesterol esters or free cholesterol
What are the reasons for HDL being better than LDL?
- HDL contains less TAG
- LDL is larger => plaque formation
- HDL fxn is to remove free cholesterols in the blood whereas LDL delivers cholesterol to peripheral tissues
- LDLs can be oxidize => plaque formation
- HDLs are atheroprotective b/c contain antioxidant enzyme to prevent LDL oxidation
What is the difference between chylomicron and chylomicron remnant function?
- chylomicrons transport dietary TAG from the intestine
- chylomicron remnants have exchanged TAG and sent CE to the HDL and deliver TAG to the liver
What changes about the contents of lipoproteins as you go from VLDL => IDL => LDL?
VLDL = mostly TAG LDL = more cholesterol
Where do VLDL/IDL/LDL deliver TAG and Cholesterol to?
VLDL => TAG to adipose, skeletal muscle, heart muscle,
IDL/LDL => Cholesterol to liver, macrophages, and peripheral cells
Describe the chylomicron:
- source
- main lipid
- integral apo
- function
- made in intestine
- mainly TAG
- B48
- transports dietary TAG to adipose and other tissues
Describe the chylomicron remnant.
- source
- main lipid
- integral apo
- function
- made after C2/E exchange with HDL
- TAG
- B48
- delivers remaining dietary TAG to liver
- exchanges TAG for CE with HDL and delivers those to liver
Describe the VLDL.
- source
- main lipid
- integral apo
- function
- liver
- TAG
- B100
- delivers endogenously synthesized lipids to adipose, heart, and skeletal muscle
- exchanges TAG for CE with HDL
Describe the IDL
- source
- main lipid
- integral apo
- function
- VLDL remnant; formed in circulation
- TAG and cholesterol
- B100
- delivers remaining TAG and cholesterol to liver
- exchanges TAG for CE with HDL
Describe LDL.
- source
- main lipid
- integral apo
- function
- IDL remnant; formed in circulation
- cholesterol
- B100
- delivers cholesterol to the liver and other steroidogenic cells
Describe HDL.
- source
- main lipid
- integral apo
- function
- made in the liver
- cholesterol
- A1
- accepts cholesterol from peripheral cells and esterifies it. returns CE to the liver
- exchanges its CE for TAG from other lipoproteins in circulation
- atheroprotective peroxonase antioxidant for LDL
- apoprotein reservoir
What does LPL do? What is required?
LPL = lipoprotein lipases
- degrades TAGs in lipoproteins marked with C2 to release glycerol and FFAs
- glycerol goes back to the liver
- FFAs go to skeletal and cardiac muscle
What is the function of B100?
- marks VLDL, IDL, LDL
- binds LDL receptor
What is the function of A1?
- marks HDL
- activates LCAT (cholesterol esterification)
- binds to HDL receptor
What is the function of C2?
- exchanged from HDL to other lipoproteins
- activates LPL
What is the function of E?
- exchanged from HDL to other lipoproteins
- binds to LDR-Receptor-like Protein (LRP)
- binds to remnant receptor
What is the function of B48?
- marks chylomicrons
List the development and mechanism of chylomicron function.
- chylomicrons take dietary TAG from intestines
- nascent chylomicrons express B48
- apoprotein exchange with HDL => mature chylomicron now also expresses C2 and E
- LPL is activated => TAG breakdown, C2 used
- remnant chylomicron enters liver via E binding to LRP and LDLR
List the development and mechanism of VLDL/IDL/LDL function.
- liver synthesized TAG are packaged into VLDL
- VLDL expresses B100
- transient exchange with HDL => VLDL now expresses C2 and E
- LPL activated => IDL
- IDL is smaller, contains less TAG
- LPL activated again => LDL
- LDL expresses only B100; C2 and E are returned to HDL
- B100 binds to LDLR on peripheral tissues, macrophages, and liver
Describe the relationship between cholesterol biosynthesis and LDLR regulation.
- if increased cholesterol biosynthesis (increased cholesterol levels), decreased LDLR (downregulation)
- if decreased cholesterol biosynthesis (decreased cholesterol levels), increased LDLR (upregulation)
How do statins affect LDLR regulation?
- block HMG-CoA reductase
- decreased cholesterol biosynthesis
- increased LDLR upregulation
- increase removal of cholesterol from bloodstream
What are the 2 pathways of LDL uptake? Which is the major?
major = LDLR-mediated endocytosis minor = LDLR-independent uptake by macrophages
Why is the minor LDL uptake pathway important?
in times of high cholesterol, LDLR-dependent uptake is decreased b/c LDLR is downregulated. But LDLR-independent uptake is still active and contributes to cellular LDL uptake
Describe the mechanism by which oxidized LDL contributes to CAD.
- oxidized LDL uptake by macrophages due to LDLR-independent uptake or oxidized LDLR
- cholesterol increase in macrophages => become foam cells
- foam cell accumulation and cytokines causes smooth muscle proliferation and calcification
- continued LDL uptake leads to atherosclerosis
Describe the mechanism of how HDL transport works.
- nascent HDL with A1, C2, and E made by liver
- A1 activates LCAT which esterifies the cholesterol taken up from peripheral cells
- mature HDL with cholesterol esters and HDL returns to liver
What should your total cholesterol level be?
Total cholesterol = …
HDL + LDL + 20% TAG
What should your total HDL be?
> 60 mg/dL
What should your total LDL be?
What should your TAG levels be?
What is the optimal total:HDL ratio?
200:60 = 3.3.:1
