Lipoproteins

Question 1

Can we use plant sterols for cholesterol synthesis?

Answer 1

Not really, but the consumption of plant sterols blocks update of cholesterol in the intestine

Plant sterol metabolites can be absorbed and used to make cholesterol though

Question 2

Lipoprotein density from least dense to most

Major lipids in each

Answer 2

Chylomicron —> VLDL —> IDL —> LDL —> HDL (some HDL are denser than water)

TAGs. TAGs. CE. CE. Phospholipids

Question 3

ApoA types, related lipoproteins and functions

Answer 3

ApoA-I on CM and HDL (helps HDL to pinch off CM with redundant PL)
- Acts in structure and LCAT activator

ApoA-II on CM and HDL (same)
- unknown function

ApoA-III on CM and HDL
- LCAT activator, satiety and other functions unknown

Question 4

ApoB types, related lipoprotein and functions

Answer 4

ApoB-48 on CM
- transport of CM and structure
- synthesized by the intestine as a ApoB-100 that is stopped at 48% (RNA editing)

ApoB-100 on VLDL, IDL, LDL
- structure, VLDL transport and LDLreceptor ligand
- synthesized in the liver

Question 5

ApoC types, lipoproteins associated with and functions

Answer 5

ApoC-I on CM, VLDL, IDL, LDL
- unknown function

ApoC-II on CM, VLDL, IDL, LDL
- lipoprotein lipase activator

ApoC-III on CM, VLDL, IDL, LDL
- lipoprotein lipase inhibitor

Question 6

ApoE types, lipoproteins associated and functions

Answer 6

ApoE on CM, VLDL, IDL, LDL
- ligand for LDLreceptor and VLDL receptor

Question 7

Nascent chylomicrons and mature chylomicrons contain

Answer 7

Nascent: Triglycerides, cholesterol/CE, ApoB-48

Mature: TAGs, CE/cholesterol, ApoA-I, ApoB-48, ApoE and ApoC-II
- ApoE and ApoC-II come from an HDL

Question 8

Chylomicron remnant contains

Answer 8

Less cholesterol esters, cholesterol, phospholipids, and TAGs
Contains ApoB-48 and ApoE (receptor on liver)
ApoC-II and ApoA-I go to HDL

Question 9

What is abetalipoproteinemia ?

Answer 9

Lack of apoB-48 and/or apoB-100

Question 10

What is hyperlipoproteinemia?

Answer 10

Type I - deficiency of ApoC-II (can’t hydrolyze TAGs in lipoproteins)
Type II - deficiency ApoE (can’t absorb lipoproteins into the liver for breakdown)

Question 11

Explanation of atherosclerosis

Answer 11

High cholesterol causes cells to block cholesterol uptake
Macrophages consume excess LDL and eventually die
Dead macrophages accumulate in injury blood vessels and create blockages

Question 12

VLDL contains

Answer 12

Cholesterol/CE and TAGs from liver
ApoB-100, ApoC-II, ApoE

ApoC-II is transferred back to HDL to form IDL

Question 13

IDL contains

Answer 13

ApoE, ApoB-100, decrease TAGs, high cholesterol

TAGs exchanged with HDL and CE accepted via CETP, and ApoE is lost to become LDL

Question 14

What is tangier disease?

Answer 14

Rare autosomal disease with defective ABCA1 transporter needed for cholesterol and phospholipid uptake by nascent HDL and cells (lacking HDL as a result and increased intracellular free cholesterol)

Question 15

Role of nascent HDL

Answer 15

Produced in liver and small intestine
Contains ApoA-I, picks up cholesterol in coating (unless Tangier disease)
LCAT esterifies cholesterol into CE
HDL delivers CE to liver, VLDL and IDL
HDL receives TAGs and PL from VLDL/IDL/LDL to return to liver

Question 16

HDL trades apolipoproteins with which lipoproteins?

Answer 16

HDL trades ApoC-II and ApoE with chylomicrons and VLDL for activating lipoprotein lipase (ApoC-II) and binding liver receptors

Question 17

Reverse cholesterol transport pathway with HDL

Answer 17

Unesterified cholesterol can be directly dropped off at liver by HDL
Esterified cholesterol is passed to lipoproteins by CETP which can then drop the CE off to be converted to UC

Question 18

Attributes of adipocytes/lipocytes that makes weight loss difficult

Answer 18

Adipocytes can live up to 4 years
Once they are terminally differentiated, they are very efficient at taking up fat store

Question 19

How does the cell respond to increased cholesterol concentration?

Answer 19

LDL binds to cell receptors in coated pits on target cell
Lysomes break down LDL into components, cholesterol is brought to the ER
1. Reduction in HMG-coA reductase expression through SREBP pathway
2. ACAT convert cholesterol to CE to be stored in vesicles in cytoplasm
3. leads to suppression of LDL receptors on the cell
4. Increased ABCA1 expression to move UC to HDL

Question 20

About the LDL receptor

Answer 20

Very complex, multi-domain receptor
Interfaces with ApoE
SNPs in receptor polypeptides can affect receptor sensitivity to LDL

Question 21

In a cell increased free cholesterol leads to:

Answer 21

1. Decreased HMGR production via SREBP pathway
2. Decreased expression of LDL receptors
3. Increased ACAT (acyl-coA cholesterol acetyltransferase) converting free cholesterol –> cholesterol esters
4. Increased expression of ABCA1 to move cholesterol to HDL particles (unless Tangier disease)

Question 22

In a liver (parenchymal cell) free cholesterol can go which pathways?

Answer 22

1. UC –> VLDL
2. ACAT converted to CE for storage in droplets in cytoplasm
3. Secreted directly into bile as free cholesterol
4. Bile acids production involving Cyp7a1

Question 23

Conversion of cholesterol into bile acids pathway

Answer 23

1. Cholesterol –> 7alpha-hydroxycholesterol, by 7alpha hydroxylase
2. 7alpha-hydroxycholesterol –> Chenodeoxycholic acid and cholic acid
3. Addition of taurine or glycine

Question 24

What is the rate limiting step of bile acid production from cholesterol?

Answer 24

Cholesterol –> 7alpha-hydroxycholesterol

7alpha hydroxylase/Cyp7a1

In most animals cholesterol stimulates this step, but not in humans, in humans it is stimulated by LXR bound by oxysterols
Bile acids repress this enzyme

Question 25

Types of cholesterol esters to know?

Answer 25

Cholesteryl linoleate - form inside LDL core
Cholesteryl oleate - form inside cells for storage in cytoplasm (bioactively inert)