Lipoproteins I & II

Free cholesterolin the liver stimulates two different processes, what are they?

1) It stimulates ACAT, this forms cholesteryl esters which are formed in liver cytosol and are stored. 2) Free cholesterol also stimulates 7-alpha hydroxylase for bile acid synthesis.

Other than the remanant receptors. How else can IDL be taken up into the liver? 2 other ways...

1) LDL receptor related protein. LRP 2) LDL receptor which needs ApoB100/ApoE

Where is LPL mainly synthesized?

1) Myocardial cells 2) Fat cells 3) Skeletal muscle cells

Where is SR-B1 found besides the liver?

1) Steroidegenic tissues 2) Macrophages for the release of cholesterol esters

What is the % of LDLs taken up into the liver?

70% of LDLs are taken up by the liver via LDL-receptors. The rest is distributed via the blood to cells

Which membrane transporter is involved with the release of free cholesterol from plasma membranes into the blood?

Cholesterol ABC transporters.

Which two lipoproteins are TAG-rich? Which lipoprotein contains dietary lipids?

Chylomicrons and VLDL are TAG-rich lipoproteins. Chylomicrons contain dietary lipids, mostly TAGs (~90%), but also vitamins.

How are free fatty acids transported through the blood?

Complexed with albumin

Which common disease leads to acquired hypertriacylglycerolemia?

Diabetes and hypertension

Which lipoprotein has the highest percentage of proteins and is the smallest?

HDL has the highest percentage of proteins and it is the smallest.

Which lipoproteins are elevated in... Type I hyperlipidemia Type IV hyperlipidemia Type V hyperlipidemia

Type I= Chylomicrons Type IV= VLDL Type V=Both chylomicrons and VLDL accumulate

What is the difference between hyperlipidemia Type IIa and type IIb? Are they common?

Type IIa is characterized by high LDL. Type IIb is characterized by high LDL and high VLDL. Yes both are relatively common.

What is HDL also known by?

alpha-lipoprotein

Which lipoproteins are mainly involved with CETP transfer?

VLDL and HDL. VLDL gives its TAGS to HDL and HDL gives its cholesteryl esters to VLDL.

Hypoalphalipoproteinemia

Very low serum HDL levels, it can be aquired

How do dietary lipid-soluble vitamins and dietary essential FA in TAGs reach the liver?

Via chylomicron remnants

How are TAGs and cholesteryl esters transported in the blood?

Via inside lipoproteins

IDL are taken up in the liver via which type of receptor? What must they recognize?

Via remanant receptors. They recognize the Apo E.

HDL 2 delivers cholesterol to the liver via which receptor?

Via scavenger receptor SR-B1

HDL2 delivers cholesterol to the liver via which receptor?

Via the scaveger receptor SR-B1

What is VLDL also known by?

pre Beta-lipoprotein

How do oxLDL accumulate in macrophages?

via scavenger receptor SR-A. This leads to foam cells

Which three major apoproteins are found in the phospholipid monolayer of HDL? Which two are activating enzymes, which one is needed for receptor recognition?

1. apo A-1 activates LCAT. 2. apo C-II activates lipoprotein lipase. 3. apo E is needed for remnant receptor recognition.

Normal level fasting TAGs is about... Majority of TAGs are found in...

100-150 mg/dL Majority is found in VLDL

What is the % for the uptake of IDLs into the liver?

50% of IDLs are taken up. The rest is used to form LDL by hepatic lipase which is bound in the capillaries

Abetalipoproteinmia is caused by what?

A genetic defect in microsomal TAG transfer protein MTP.

What is discoidal nascent HDL?

A newly formed HDL that is not filled with cholesteryl esters, has a discoidal shape.

A hypolipodemia resulting in low levels of apo B-100 apo B-48. Which results in very low levels of VLDL, LDL and chylomicrons

Abetalipoproteinemia

Describe cholesterol ester transfer protein? (CETP)

Allows the exchange of cholesteryl esters for TAGs btwn lipoproteins in the blood.

When compared to electrophoresis of serum proteins, HDL is separated like...

Alpha-globulins

Which apoprotein is used for the HDL function of reverse cholesterol transport?

Apo A-1 It is also the main apoprotein found in HDL.

Which apoprotein is needed by hepatocytes to release VLDL into the blood?

Apo B-100

This molecule is synthesized in the intestinal mucosal cells and is needed for release of chylomicrons into the lymph.

Apo B-48

Which apoprotein is needed by intestinal mucosal cells to release chylomicrons into the lymph?

Apo B-48

Which apoprotein is needed for the activation of lipoprotein lipase and which apoprotein is needed for the activation of lecithin:cholesterol acyltransferase (LCAT)?

Apo C-II activates lipoprotein lipase. Apo A-1 activates LCAT and is found in HDL and allows the reverse cholesterol transport.

What does lipoprotein lipase needs for its activation?

Apo C-II which is found in VLDL and chylomicrons and was delivered by HDL

What is the most common isoform of Apo E?

Apo E-3

This molecule is synthesized in the liver and is needed for release of VLDL into the blood

ApoB 100

When compared to electrophoresis of serum proteins, LDL is separated like...

Beta-globulins

What is LDL also known by?

Beta-lipoprotein

Lipoprotein lipase is found where?

Bound in capillaries of the heart, adipose tissue, skeletal muscle.

Hepatic Lipase is found where?

Bound in capillaries of the liver

What are the substrates of ACAT?

Fatty acyl-CoA and free cholesterol

Describe the process of going from discoidal HDL to HDL-3 and finally HDL-2?

Firstly, HDL-3 is formed from the discoidal HDL after uptake of cholesteryl esters. Once HDL-3 is filled with more cholesteryl esters and after uptake of phospholipids, then the larger HDL-2 is formed. It is HDL-2 that delivers cholesteryl esters to the liver.

After binding to the SR-B1 receptor on liver. The phospholipid bilayer is opened by what enzyme?

Hepatic lipase

Which lipase cleaves both TAG and phospholipids?

Hepatic lipase cleaves both.

Similar to LPL this lipase is found in the liver instead.

Hepatic lipase is found in the capillaries of the liver. Its activation, unlike LPL which needs ApoCII, is still under investigation.

Abnormally high serum levels of lipoprotein remnants or of LDL.

Hypercholesterolemia

Genetic deficiency of LDL-receptors is found in...

Hyperlipidemia type II

Abnormally high serum levels of chylomicrons and VLDL.

Hypertriacylglycerolemia

oxLDL accumulate where?

In macrophages

Where is LPL found in the highest concentration?

In the capillaries of the heart

Hormone sensitive lipase is found where?

Inside of fat cells

Where is LPL synthesized?

Inside of myocytes or adipocytes

Where is LPL found?

LPL is anchored via GAGs to the endothelial surface of these cells and does not travel with the blood stream.

Where is LCAT's site of action?

It acts on plasma membranes to get rid of the free cholesterol.

What does CETP do? Why is it important?

It allows the transfer of TAGs from VLDL into HDL in exchange for cholesteryl esters. it improves the function of LCAT by preventing product inhibition.

What does hepatic lipase do and where is it found?

It cleaves TAGs from IDL and is found in hepatic capillaries

What does LCAT do?

It converts cholesterol into cholesterol esters. This allows the transport of cholesterol esters within the lumen of HDL

What is MTP responsible for?

It interacts with APoB and is needed for the formation of VLDL and chylomicrons

What is Lp(a)?

It is an abnormal LDL with the protein apo (a) linked to Apo B-100 via a disulfide bond. This leads to a special structure of Kringle to be found. It is a structural analog to plasminogen and can inhibit dissolution of blood clots.

What is APO CII?

It is found on HDL. Transferred from HDL to VLDL and chylomicrons Needed for activation of lipoprotein lipase

At high cytosolic cholesterol levels the SCAP-SREBP complex is retained where? What does this do?

It is retained in the ER. This prevents it from going into the nucleus. Cholesterol synthesis and uptake of cholesterol is reduced.

Where in the body is LCAT synthesized?

It is synthesized in the liver and released into the blood stream.

What does the ABCA1 transporter do?

It moves cholesterol from the inner leaflet to the outer leaflet where it can act as a substrate for LCAT

What does LCAT need for activation?

It needs Apo A-1

Where does LCAT get the fatty acid it uses for esterfication of cholesterol?

It uses the fatty acid in position 2 phosphotidylcholine of the HDL monlayer.

What activates LCAT and where is it found?

LCAT is activated by APO A-1 and APO A-1 is found on HDL molecules.

Where is LCAT found and how is this different from ACAT?

LCAT is located extracellular in blood and synthesized by the liver. LCAT esterifies cholesterol so that the cholesterol found in the outer layer of the phospholipid bilayer can enter the HDL molecule. HDL contains an important lipoprotein known as Apo A1 which activates LCAT and allows for this process to happen. ACAT is located in the cytosol of cells. It is responsible for trapping cholesterol within the cell by converting it to a cholesterol ester.

Which lipoprotein has the highest percentage of cholesterol plus cholesteryl esters?

LDL has the highest percentage of cholesterol plus cholesteryl esters

How are LDL-A and LDL-B different? Which one is considered a risk factor for atherosclerosis?

LDL-A is larger than LDL-B. LDL-B is a risk factor as it is smaller and can be trapped in the ECM

LDL-receptors need this apoprotein to recognize LDL and uptake it.

LDL-receptors need only apo B-100 for LDL recognition. Uptake is via endocytosis of both, LDL and the LDL-receptor.

How are macrophages changed to foam cells? What is released by foam cells and stimulates the migration of smooth muscle cells?

Macrophages that take up excess oxLDL become foam cells. oxLDL are mostly filled with cholesteryl esters. Foam cells release growth factors and cytokines

Are oxLDL recognized by the LDL-receptor?

No they are recognized by the LDL receptor

Once fatty acids are uptaken in fat cells, do they undergo B-oxidation within the fat cells?

No, in fat cells they are taken up and mainly used to synthesize TAGs for storage.

What are the enzymes that reduce LDL oxidation?

Paraoxonase PAF acetylhydrolase

What are the substrates of LCAT?

Phosphatidylcholine of the HDL monolayer and free cholesterol.

The transport of cholesterol from extra hepatic cells to the liver is named... What enzyme does it involve?

Reverse Cholesterol transport LCAT

Compare the SR-B1 found in liver to the SR-A found in macrophages!

SR-B1 in liver binds to HDL-2 which deliver cholesteryl esters to the liver. SR-A is a scavenger receptor for oxLDL found in macrophages which takes up the total oxLDL. This uptake is not regulated and leads to foam cells.

A heridatary disease that leads to very low serum HDL. Orange tonsils. Defect in cholesterol ABC transporter in plasma membrane.

Tangier disease

If nascent HDL is not filled what disease results?

Tangier disease

Which apoprotein is needed for the release of VLDL from the liver into the blood? Which apoproteins are found in IDL?

The release of VLDL into the blood from the liver needs apo B-100 IDL contain apo E and apo B-100.

Which apoprotein is needed for the release of chylomicrons from intestinal cells into the lymph? Which apoproteins are found in chylomicron remnants?

The release of chylomicrons into the lymph needs apo B-48. The chylomicron remnants contain apo B-48 and apo E

What does it mean when one says free cholesterol can be "rubbed"?

This free cholesterol can be "rubbed" into the phospholipid monolayer of HDL. This can handle, however, only limited amounts, and the free cholesterol is used by LCAT to form larger amounts of cholesteryl esters in blood.

What is the purpose of chylomicron remnants?

To deliver dietary cholesteryl esters, lipid soluble vitamins and some TAGs back to the liver.

Electrophoresis separates proteins according to their...

To their overall charge and not size

What is the purpose of LDL?

To transport cholesteryl esters in the blood and deliver cholesterol to cells that need it for plasma membranes of steroid hormone synthesis.

What stimulates LDL to become oxLDL?

oxidants