Metabolism 9

Question 1

How are lipids transported in plasma?

Answer 1

Lipids Are Transported in Plasma as Lipoproteins That Are Composed of Apolipoproteins and Lipids.

Question 2

For chylomicron (formed in intestines), What is the main lipid? Apopoproteins? Function?

Answer 2

Formed: in intestines

Main Lipid: TAG

Apoproteins: B-48 (A,C,E)

Function: transports dietary TAG to adipose and other tissues

Question 3

For Chylomicron Remnant,

What is the main lipid? Apopoproteins? Function?

Answer 3

Main Lipid: TAG

Apoproteins: B-48 (A,C,E)

Function: delivers remaining dietary TAG to liver. Exchanges TAG for CE from HDL; delivers CE to the liver

Question 4

For VLDL, where is it formed? What is the main lipid? Apopoproteins? Function?

Answer 4

Formed: in liver

Main Lipid: TAG

Apoproteins: B-100 (A,C,E)

Function: Transports endogenously synthesized TAG to adipose tissue and to skeletal and heart muscle. Exchanges TAG for CE from HDL

Question 5

For IDL-VLDL remnant where is it formed? What is the main lipid? Apopoproteins? Function?

Answer 5

Formed: formed via processing of VLDL in the circulation

Main Lipid: TAG and cholesterol

Apoproteins: B-100, E

Function: Delivers remaining TAG and cholesterol to
the liver.
Exchanges TAG for CE from HDL. Delivers
CE to the liver

Question 6

For LDL, where is it formed? What is the main lipid? Apopoproteins? Function?

Answer 6

Formed: (formed via processing of IDL in the circulation)

Main Lipid: cholesterol

Apoproteins: B-100

Function: Delivers cholesterol to the liver and other cells, including steroidogenic cells

Question 7

For HDL, where is it formed? What is the main lipid? Apopoproteins? Function?

Answer 7

Formed: (formed in the liver;
some formed in intestines)

Main Lipid: cholesterol

Apoproteins: A’s (C,E)

Function: Accepts cholesterol from peripheral cells,
esterifies it, and transports CE’s to liver
Exchanges CE for TAG in VLDL, IDL and chylomicron remnants.
Atheroprotective via enzymes such as paraoxonase that inhibit LDL oxidation
Serves as reservoir for circulating apoproteins (A,C,and E), which are
transported to other lipoprotein particles.

Question 8

Describe the organs and pathways involved with lipoprotein metabolism.

Answer 8

Slide 12

p 4

Question 9

What is the major LP for B-48? Function?

Answer 9

chylomicron (CyM)

Function: chylomicron secretion

Question 10

What are the major LPs for B-100? Function?

Answer 10

VLDL
LDL
IDL

Binds LDL Receptor, VLDL secretion

Question 11

What is the major LP for A-1? Function?

Answer 11

HDL

Activates LCAT (lecithin: cholesterol acyl transferase) and binds HDL receptor

Question 12

What are the major LPs for C-II? Function

Answer 12

CyM, IDL, VLDL, HDL

cofactor that activates LP lipase

Question 13

What is the major LP for Apoprotein E? Function?

Answer 13

CyM, VLDL, IDL

clearance via binding to LRP (LDL receptor associated protein)

Question 14

Which aporoteins are cofactor for enyzmes?

Answer 14

Apo-CII: lipoprotein lipase

Apo-AI: lecithin: cholesterol acyltransferase (LCAT)

Question 15

Which apoprotein are Apoliprotein ligands for extracellular receptors?

Answer 15

Apo E: Binds to LRP
Apo B-100: Binds to LDL receptor
Apo A-I: Binds to HDL receptor

Question 16

Which apoproteins are in lipoprotein particles?

Answer 16

Apo B-48: Chylomicrons
Apo B-100: VLDL, IDL, LDL
Apo A-I: HDL

Question 17

Describe chylomicron metabolism.

Answer 17

1. Chylomicrons transport dietary TA and cholesterol.
2. Nascent chylomicrons are synthesized in the intestines along with Apo A-1 and Apo B-48.
3. Chylomicrons transiently gain Apo-E and Apo C-II from HDL in the plasma.
4. Apo C-II activates lipoprotein lipase (LPL), located on capillary endothelia. LPL catalyzes
   the conversion of TAGs to free fatty acids and glycerol. Fatty acids are taken up by tissues
   and metabolized.
5. Chylomicron remnants are removed by liver via receptor-mediated endocytosis. This
   involves Apo E, which binds to the LDL receptor and LDL receptor related protein (LRP)
6. HDL serves as a repository for Apo C-II, A-I, and E.

p 6, slides 20-21

Question 18

Draw a flow chart for Very Low Density Lipoproteins(VLDL) Transport Triacylglycerols (TAGs) and Cholesterol (C) That Are Synthesized Endogenously.

Answer 18

Slide 22 p 7

Question 19

What do VLDL transport?
What is VLDL a precursor for?

Where are VLDL synthesized (with what else)?

What does VLDL pick up in the circulation?

What does C-II do?

Answer 19

1. VLDL transport TAGs and cholesterol that are synthesized endogenously. VLDL also serve as the precursor of IDL and of LDL.
2. VLDL are synthesized in the liver along with Apo B-100. VLDL picks up Apo E and Apo C-II from HDL in the
   circulation.

Apo C-II activates lipoprotein lipase (LPL), which catalyzes the conversion of TAGs to glycerol and FFA.

Question 20

How to VLDL become IDL?

What happens in the conversion of VLDL to IDL?

What happens in the conversion of IDL to LDL?

What happens to remaining LDL?

Answer 20

As VLDL lose TAG and shrink, they are converted to IDL (intermediate density lipoproteins). IDL are also known as the VLDL remnant.

In the conversion of VLDL-> IDL-> LDL, Apo C-II activates lipoprotein lipase (LPL), which cleaves TAGs into
free fatty acids (FFA) and glycerol. FFA are taken up by tissues and metabolized.

In the conversion of IDL-> LDL, Apo C-II and Apo E are transferred to HDL. LDL retains Apo B-100.

Any remaining IDL can be removed from the circulation via receptor-mediated endocytosis, which involves the LDL receptor (via binding to Apo B-100 and to Apo E) and LRP (via binding to Apo E). LRP = LDL receptor related protein

Question 21

What is the major pathway by which LDL is removed from the circulation?

Answer 21

The major pathway by which LDL is removed from the circulation involves the binding of Apo B-100 on LDL to the LDL receptor. LDL receptors are found on both hepatic and nonhepatic tissues.

The major mechanism for removal of LDL requires a functional LDL receptor

See diagram p 8

Question 22

What happens when cholesterol levels are high to the LDL receptors?

Answer 22

When cholesterol levels are high, there is a down-regulation of the high affinity LDL
receptors that are involved with LDL receptor-mediated uptake of cholesterol. These
cellular adaptations occur when the cell has adequate cholesterol.

However, even in the presence of high cholesterol levels, the non-specific receptorindependent
pathway (pinocytosis) contributes to cellular uptake of LDL cholesterol. Although not a major pathway under conditions when cholesterol levels are normal, this pathway can assume greater importance when LDL cholesterol levels are high.

Question 23

Describe the Uptake of Oxidized Cholesterol by Macrophages & Coronary Artery Disease:

What substances can oxidize LDL cholesterol? What can prevent oxidation?

How can oxidized LDL be taken up?

What happens next?/ with continued uptake of oxidized LDL?

Answer 23

1. LDL cholesterol can be oxidized by oxidants (superoxide, nitric oxide, hydrogen peroxide.

Vitamin E, ascorbic acid (vitamin C), B-carotene (vitamin A), and other antioxidants
can prevent such oxidation.

2. Oxidized LDL can be taken up by macrophages. It has been hypothesized that the
   mechanism could involve a relatively minor pathway that utilizes oxidized LDL receptors
   and/or the receptor-independent pathway (above). The cholesterol-laden macrophages
   become foam cells.
3. Foam cells accumulate, release cytokines that stimulate the proliferation of smooth muscle cells and calcification of plaque.
4. Continued uptake of oxidized LDL leads to coronary artery disease and
   atherosclerosis.

Question 24

Where are nascent HDL’s synthesized? What shape are they secreted in? What do they contain?

Answer 24

Nascent HDLs are synthesized in the liver (and small intestines) and secreted with a discoidal shape. They contain Apo A-I, LCAT and phospholipids.

Question 25

What is purpose of HDLs?

Answer 25

HDLs serve as a reservoir of apoproteins for chylomicrons and VLDL.

Question 26

How do HDLs change as they accumulate cholesterol from peripheral tissues and other lipoproteins?

Answer 26

HDLs are rapidly converted to a spherical shape as they accumulate cholesterol from peripheral tissues and other lipoproteins.

Question 27

What happens to free (non-esterified) cholesterol? When/how does it become esterified?

Answer 27

Free (nonesterified) cholesterol is transferred from plasma membranes to lipid poor nascent HDL yielding HDL3; this is mediated by ABCA-1. HDL3 + additional free cholesterol to HDL2. Once free cholesterol is taken up by HDL, the enzyme PCAT (also called LCAT) esterifies the cholesterol. This enzyme is activated by Apo A-1.

Question 28

What does mature HDL do?

Answer 28

Mature HDL deliver cholesterol to the liver for excretion (reverse cholesterol transport) by two mechanisms.

Question 29

Mature HDL deliver cholesterol to the liver for excretion (reverse cholesterol transport) by two mechanisms. Describe both.

Answer 29

a). CETP mediates the transfer of cholesterol esters from HDL’s to VLDL & IDL & chylomicron remnants in exchange for TAG. This produces a larger HDL2. Cholesterol enriched IDL and chylomicron remnants are taken up by the liver via Apo E-dependent binding to the LDL receptor and LRP. b). Spherical HDLs are taken up by liver by receptor-mediated endocytosis via Apo AI dependent binding to the scavenger receptor protein BI (SR-BI).

Question 30

What happens to cholesterol that is delivered to the liver?

Answer 30

Cholesterol that is delivered to the liver is then either converted to bile acids or repackaged into lipoproteins.

Question 31

Describe the additional atheroprotective effects of HDL.

Answer 31

a) . HDL contains enzymes, i.e., paroxonase, that inhibit LDL oxidation in intima of blood vessels. b) . HDL increases NO synthesis by endothelial cells.

Question 32

LDL/HDL; which is good/bad cholesterol? Explain.

Answer 32

-LDL has more lipids more CE, size! HDL is smaller, LDL is larger. LDL contributes way more than HDL when you are fat function of HDL and LDL v imp and det. why good/bad both syn. in liver. LDL takes TAG and CE to transport across body then back to liver. HDL sun in liver and destroyed to liver. job to bring CE back to liver. LDL in blood means supplying to organs and can influence blood formation LDL can undergo oxidation-smoking can cause oxidation of LDL. promote formation of clots LDL undergo oxidation compared to HDL. enzyme can act as antioxidant. HDL do not undergo oxidation transportering to or transporting IN to liver.