Metabolism: Lipoproteins Flashcards

1
Q

Which lipoprotein has the highest protein:lipid ratio? the lowest?

A
high = HDL
low = chylomicron
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2
Q

Describe the structure of a lipoprotein.

A

core = TAG and cholesterol esters
membrane = phospholipids and free cholesterol
peripheral apoproteins = exchangeable
integral apoproteins = indicative of lipoprotein type

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3
Q

Where are lipoproteins made? What is the difference between these kinds?

A
liver = endogenous synthesis of TAG, cholesterol
intestines = dietary
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4
Q

What is the density of the lipoproteins referring to?

A

density of proteins
HDL = high protein content
hence, HDL is more negative

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5
Q

Compare the structures of chylomicrons, VLDL, LDL, and HDL.

A

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

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6
Q

What are the reasons for HDL being better than LDL?

A
  • 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
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7
Q

What is the difference between chylomicron and chylomicron remnant function?

A
  • chylomicrons transport dietary TAG from the intestine

- chylomicron remnants have exchanged TAG and sent CE to the HDL and deliver TAG to the liver

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8
Q

What changes about the contents of lipoproteins as you go from VLDL => IDL => LDL?

A
VLDL = mostly TAG
LDL = more cholesterol
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9
Q

Where do VLDL/IDL/LDL deliver TAG and Cholesterol to?

A

VLDL => TAG to adipose, skeletal muscle, heart muscle,

IDL/LDL => Cholesterol to liver, macrophages, and peripheral cells

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10
Q

Describe the chylomicron:

  • source
  • main lipid
  • integral apo
  • function
A
  • made in intestine
  • mainly TAG
  • B48
  • transports dietary TAG to adipose and other tissues
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11
Q

Describe the chylomicron remnant.

  • source
  • main lipid
  • integral apo
  • function
A
  • 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
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12
Q

Describe the VLDL.

  • source
  • main lipid
  • integral apo
  • function
A
  • liver
  • TAG
  • B100
  • delivers endogenously synthesized lipids to adipose, heart, and skeletal muscle
  • exchanges TAG for CE with HDL
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13
Q

Describe the IDL

  • source
  • main lipid
  • integral apo
  • function
A
  • VLDL remnant; formed in circulation
  • TAG and cholesterol
  • B100
  • delivers remaining TAG and cholesterol to liver
  • exchanges TAG for CE with HDL
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14
Q

Describe LDL.

  • source
  • main lipid
  • integral apo
  • function
A
  • IDL remnant; formed in circulation
  • cholesterol
  • B100
  • delivers cholesterol to the liver and other steroidogenic cells
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15
Q

Describe HDL.

  • source
  • main lipid
  • integral apo
  • function
A
  • 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
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16
Q

What does LPL do? What is required?

A

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
17
Q

What is the function of B100?

A
  • marks VLDL, IDL, LDL

- binds LDL receptor

18
Q

What is the function of A1?

A
  • marks HDL
  • activates LCAT (cholesterol esterification)
  • binds to HDL receptor
19
Q

What is the function of C2?

A
  • exchanged from HDL to other lipoproteins

- activates LPL

20
Q

What is the function of E?

A
  • exchanged from HDL to other lipoproteins
  • binds to LDR-Receptor-like Protein (LRP)
  • binds to remnant receptor
21
Q

What is the function of B48?

A
  • marks chylomicrons
22
Q

List the development and mechanism of chylomicron function.

A
  1. chylomicrons take dietary TAG from intestines
  2. nascent chylomicrons express B48
  3. apoprotein exchange with HDL => mature chylomicron now also expresses C2 and E
  4. LPL is activated => TAG breakdown, C2 used
  5. remnant chylomicron enters liver via E binding to LRP and LDLR
23
Q

List the development and mechanism of VLDL/IDL/LDL function.

A
  1. liver synthesized TAG are packaged into VLDL
  2. VLDL expresses B100
  3. transient exchange with HDL => VLDL now expresses C2 and E
  4. LPL activated => IDL
  5. IDL is smaller, contains less TAG
  6. LPL activated again => LDL
  7. LDL expresses only B100; C2 and E are returned to HDL
  8. B100 binds to LDLR on peripheral tissues, macrophages, and liver
24
Q

Describe the relationship between cholesterol biosynthesis and LDLR regulation.

A
  • if increased cholesterol biosynthesis (increased cholesterol levels), decreased LDLR (downregulation)
  • if decreased cholesterol biosynthesis (decreased cholesterol levels), increased LDLR (upregulation)
25
How do statins affect LDLR regulation?
- block HMG-CoA reductase - decreased cholesterol biosynthesis - increased LDLR upregulation - increase removal of cholesterol from bloodstream
26
What are the 2 pathways of LDL uptake? Which is the major?
``` major = LDLR-mediated endocytosis minor = LDLR-independent uptake by macrophages ```
27
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
28
Describe the mechanism by which oxidized LDL contributes to CAD.
1. oxidized LDL uptake by macrophages due to LDLR-independent uptake or oxidized LDLR 2. cholesterol increase in macrophages => become foam cells 3. foam cell accumulation and cytokines causes smooth muscle proliferation and calcification 4. continued LDL uptake leads to atherosclerosis
29
Describe the mechanism of how HDL transport works.
1. nascent HDL with A1, C2, and E made by liver 2. A1 activates LCAT which esterifies the cholesterol taken up from peripheral cells 3. mature HDL with cholesterol esters and HDL returns to liver
30
What should your total cholesterol level be?
31
Total cholesterol = ...
HDL + LDL + 20% TAG
32
What should your total HDL be?
>60 mg/dL
33
What should your total LDL be?
34
What should your TAG levels be?
35
What is the optimal total:HDL ratio?
200:60 = 3.3.:1