Pallas- Lipoprotein Metabolism

Question 1

What is found at shell of lipoproteins?

Answer 1

1. amphipathic apolipoproteins/lipids (non-esterified cholesterol and phospholipids)

Question 2

What is found at neutral lipid core of Lipoproteins?

Answer 2

• hydrophobic lipids, triglycerides, and cholesterol esters

Question 3

How can you obtain TG and cholesterol?

Answer 3

1. exogenous (diet)

2. endogenous (de novo synthesis)

Question 4

density is _____ related to lipid content and ______ to particle size

Answer 4

• directly; inversely

Question 5

which lipoprotein classes are the primary carriers of cholesterol?

Answer 5

• LDL’s and HDL’s

Question 6

lower density lipoproteins have _____ total protein percentage

Answer 6

• decreased total protein percentage (protein is more dense than lipid, so if you’re less dense, you’re more lipid and less protein)

Question 7

What is IDL

Answer 7

• Intermediate density

- aka vldl remnant

Question 8

why is HDL good

Answer 8

• does reverse cholesterol transport to move LDL’s back to liver

Question 9

what are the five classes of apolipoproteins

Answer 9

apoA through apoE

Question 10

Name some funcitons of apolipoproteins

Answer 10

1. some bind to cell surface receptors on specific cell types to target the lipoproteins to be endocytosed by the cell

EX: ApoB-100 and ApoE

2. activators of enzymes involved in lipoprotein metabolism
   
   • ex: apoC-II –> activates lipoprotein lipase (LPL)

Question 11

Define the three lipoprotein metabolism pathways

Answer 11

1. Exogenous pathway – transport of lipids from dietary fat via chylomicrons primarily to peripheral tissues
2. endogenous pathway: transport of lipids synthesized primarily by the liver to peripheral tissues via VLDL’s
3. Reverse cholesterol transport – transport of cholesterol from the peripheral tissues to the liver of via HDL’s

Question 12

Why is reverse cholesterol transport to liver important

Answer 12

• Liver is the only organ that can get rid of cholesterol via turning into bile acids or excreting it along with bile… without this function, we just have cholesterol everywhere peripherally

Question 13

where do pathway 1 and 2 converge

Answer 13

• lipoprotein lipase stimulated by Apo C-II to:

1. release TAG to cells
2. createIDL and chylomicron remnants

Question 14

what is fate of chylomicron remnants

Answer 14

• go to liver

Question 15

what is fate of IDL remnants

Answer 15

1. goes to liver like chylomicron remnants
2. converted by hepatic lipase to lDL, where it can go to the liver OR go back to peripheral cells via receptor-mediated endocytosis

Question 16

HDL’s tend to uptake cholesterol from which cells?

Answer 16

• macrophages that have taken up cholesterol

Question 17

what important apolipoproteins are on chylomicrons?

Answer 17

1. apoB-48 – tethers remnants to heaptocytes

2. apoE – responsible for binding for uptake via endocytosis

Question 18

how are VLDL’s made? what apolipoprotein is htere?

Answer 18

• Liver… contains apoB 100

Question 19

what other apolipoproteins are a part of VLDL and how do they get there?

Answer 19

• ApoCs and apoE, along with cholesterol esters… acquired from HDL in ciruculation

Question 20

How is IDL taken up into liver?

Answer 20

• via apoE/remnant receptor

Question 21

what is the other fate of IDL? what apolipoprotein sits on it?

Answer 21

• hepatic lipase on IDL makes it lose apoE and cleave cholesterol esters to give you a lower density LDL… only has apoB-100 on it

Question 22

Name fates of low density lipoproteins

Answer 22

• MOST is uptake by liver

- rest is uptake/delivery to extrahepatic tissues

Question 23

Of the LDL’s taken up by liver, what is their fates?

Answer 23

• 3/4 receptor mediated tkaen up

1/4 non-rceptor mediated

Question 24

Of the LDL’s taken up by other tissues, what are fates

Answer 24

2/3 R mediated

1/3 non-R mediated

Question 25

what defect leads to familial hypercholesterolemia

Answer 25

• defects in LDL receptors

Question 26

What makes nascent and what is it?

Answer 26

• liver and small intestine; HDL with apoA-1

Question 27

give the first fate of HDL

Answer 27

-1. nascent HDL (newborn) becomes small HDL, goes to cells to take up cholesterol and become large HDL, whereit goes back to liver via SR-B1

Question 28

give the second fate of hdl

Answer 28

2. large HDL converted by CETP to LDL, which can then go to liver via LDL-R

Question 29

what is role of LCAT

Answer 29

• Lecithin: cholesterol acyltransferase; esterifies cholesterol to fatty acid… pushes them to center since its nonpolar and makes the cell bigger

Question 30

Why is inhibition of CETP investigated?

Answer 30

• potentially as a means of inhibiting formation of LDL to lower “bad” cholesterol and decrease risk of atheroscleoris

Question 31

relationship between coronary heart disease mortality and plasma cholesterol lvels

Answer 31

• directly correlated

Question 32

What is the result of release of cholesterol from endocytosed LDL’s?

Answer 32

1. downregulated HMG-CoA reductase
2. Downregulates LDL receptors
3. Increases ACAT (to make more HDL)