Metabolism IX: Lipoproteins

Question 1

Lipids are transported in the plasma as _________ that are composed of _________ and _________.

Answer 1

lipoproteins; apolipoproteins; lipids

Question 2

What are the 4 classes of lipoproteins?

Answer 2

• VLDL
• HDL
• LDL
• IDL

Question 3

Transports dietary TAG from the intestines to adipose tissue and other tissues (liver, heart, skeletal muscle).

Answer 3

chylomicron

Question 4

Delivers remaining dietary TAG to liver. Exchanges TAG for CE from HDL, and then delivers CE to liver.

Answer 4

chylomicron remnant

Question 5

What is the optimal TAG concentration (aka, triglyceride level in the blood)?

Answer 5

less than 150 mg/dL

Question 6

What is the optimal LDL concentration? (bad cholesterol)

Answer 6

less than 100 mg/dL

Question 7

What is the optimal HDL concentration? (good cholesterol)

Answer 7

greater than 39 mg/dL

Question 8

What is an intermediate density lipoprotein (IDL)?

Answer 8

• VLDL remnant formed via processing of VLDL in the circulation
• delivers remaining TAG and cholesterol to liver
• exchanges TAG for CE from HDL, then delivers CE to liver

Question 9

What is the common apo-protein among VLDLs, IDLs, and LDLs?

Answer 9

B-100

Question 10

What is the function of VLDLs?

Answer 10

• transport endogenously synthesized TAG to adipose tissue, skeletal muscle, heart muscle
• exchange TAG for CE from HDL

Question 11

What is the function of LDLs?

Answer 11

deliver cholesterol to liver and other cells, including steroidogenic cells; “bad” cholesterol

Question 12

What is the function of HDLs?

Answer 12

• accept cholesterol from peripheral cells, esterify it, and transport CEs to liver
• exchange CE for TAG in VLDL, IDL, and chylomicron remnants
• atheroprotective via enzymes (like paraoxonase) that can protect cells against oxidative damage
• serve as reservoir for circulating apoproteins (A, C, E)

Question 13

What are apoproteins (aka, apolipoproteins)?

Answer 13

protein components that determine the overall structures and metabolism of lipoprotein classes, and dictate interactions with receptor molecules in liver and peripheral tissues

Question 14

Chylomicrons transport _______ lipids, while VLDLs, IDLs, and LDLs transport _______ lipids.

Answer 14

exogenous (dietary); endogenous (synthesized)

Question 15

What is the apoprotein associated w/ chylomicrons vs. VLDLs, IDLs, and LDLs?

Answer 15

• CyM: B-48

- VLDL, IDL, LDL: B-100

Question 16

What is the function of the B-100 apoprotein, and what does mutation cause?

Answer 16

• function=binding LDL receptor and secreting VLDL

- mutation in B-100 is often implicated in familial hypercholesteremia and makes the body unable to clear cholesterol

Question 17

What are important co-factors for enzymes?

Answer 17

• Apo-CII: activates lipoprotein lipase

- Apo-AI: activates lecithin:cholesterol acyltransferase (LCAT)

Question 18

Apo E, Apo B-100, and Apo A-1 are ligans for which extracellular receptors:

Answer 18

chylomicron remnant receptor, LDL receptor, and HDL receptor, respectively

Question 19

Nascent chylomicrons transiently gain which apoproteins from HDL?

Answer 19

Apo E and Apo C-II

Question 20

HDL serves as a repository for which apoproteins?

Answer 20

Apo C-II and Apo E (and to a lesser extent, Apo A-1)

Question 21

How/when are VLDLs converted to IDLs?

Answer 21

They are converted to IDLs as they lose TAG and shrink.

Question 22

In the conversion of IDL–>LDL, what happens to Apo C-II, Apo E, and Apo B-100?

Answer 22

Apo C-II and Apo E are returned back to HDL, while LDL retains Apo B-100 because it is important for receptor-mediated endocytosis.

Question 23

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

Answer 23

It involves the binding of Apo B-100 on LDL to the LDL receptor on a hepatocyte.

Question 24

Receptor-independent uptake of LDL is accomplished by ______.

Answer 24

macrophages

Question 25

What does increased cholesterol of the cell lead to?

Answer 25

down-regulation of high-affinity LDL receptors, and receptor-independent uptake of LDL cholesterol (via pinocytosis)

Question 26

Is receptor-independent LDL uptake a major or minor cellular pathway?

Answer 26

It is normally a minor pathway but becomes more important when LDL cholesterol levels are high. Already having high cellular cholesterol and bringing additional cholesterol in via LDL receptors can be deleterious for the cell.

Question 27

How is LDL related to coronary artery disease?

Answer 27

• LDL cholesterol can be oxidized by oxidants
• oxidized LDL can be taken up by macrophages via pinocytosis, and macrophages become “foam cells”
• foam cells accumulate and release cytotoxins that stimulate proliferation of smooth muscle cells and calcification of plaques
• continued uptake of oxidized LDL leads to CAD and atherosclerosis

Question 28

How does HDL serve an atheroprotective effect?

Answer 28

It contains enzymes, like paraoxonase, that inhibit LDL oxidation in the tunica intima of blood vessels. It also increases NO synthesis by endothelial cells, thus vasodilating the vessels and reducing BP.