Lipid metabolism – III: Cholesterol Transport and Lipoprotein Metabolism

Question 1

What are the major apolipoproteins found in chylomicrons?

Answer 1

B-48, C-II, C-III, and phospholipids.

Question 5

What condition arises from loss-of-function mutations in Apo C-II?

Answer 5

Hypertriglyceridemia (elevated blood triglycerides).

Question 5

Which enzyme hydrolyzes triacylglycerols (TAGs) in chylomicrons, and what activates it?

Answer 5

Lipoprotein lipase (LPL), activated by apolipoprotein C-II (Apo C-II).

Question 5

What happens to free fatty acids and glycerol after chylomicron TAG hydrolysis?

Answer 5

Fatty acids are used by adipose tissue and muscles; glycerol is transported to the liver for glycolysis/gluconeogenesis.

Question 6

What causes postprandial lipemia, and how does plasma appear during this state?

Answer 6

Chylomicrons in blood after a meal; plasma appears milky white and clears after 2–2.5 hours.

Question 7

What are chylomicron remnants, and how are they taken up by the liver?

Answer 7

TAG-depleted chylomicrons containing cholesterol and apolipoproteins; ApoE facilitates liver uptake via receptors.

Question 7

What is the primary role of VLDLs, and how are they formed?

Answer 7

Transport endogenous TAGs; synthesized in the liver after carbohydrate/lipid-rich diets.

Question 7

What happens to VLDL after lipoprotein lipase acts on it?

Answer 7

VLDL is converted to IDL (intermediate-density lipoprotein).

Question 8

How is LDL formed, and why is it called “bad cholesterol”?

Answer 8

Derived from IDL after further TAG removal; high LDL levels increase atherosclerosis risk.

Question 8

What is ACAT, and what is its role in cells?

Answer 8

Acyl:cholesterol acyltransferase; esterifies cholesterol for cytoplasmic storage, preventing membrane toxicity.

Question 9

What three effects does cholesterol from LDL have on peripheral cells?

Answer 9

Inhibits HMG CoA reductase, suppresses LDL receptor synthesis, and activates ACAT for cholesterol ester storage.

Question 10

What apolipoproteins do HDLs transfer to nascent chylomicrons and VLDL?

Answer 10

Apo C-II and Apo E.

Question 11

How does HDL acquire cholesterol esters?

Answer 11

Via lecithin:cholesterol acyltransferase (LCAT), which esterifies cholesterol from peripheral tissues.

Question 12

How does HDL contribute to reverse cholesterol transport?

Answer 12

Transports cholesterol from peripheral tissues to the liver for bile salt synthesis or VLDL packaging.

Question 13

Which lipoprotein is associated with reduced cardiovascular risk, and why?

Answer 13

HDL ("good cholesterol"); removes excess cholesterol from tissues and transports it to the liver.

Question 14

Compare the core lipids and apoproteins of LDL and HDL.

Answer 14

LDL: Endogenous cholesterol esters; Apo B-100. HDL: Endogenous cholesterol esters; Apo A, C, E.

Question 15

What is the role of the LDL receptor (LDLR)?

Answer 15

Binds Apo B-100 on LDL for receptor-mediated endocytosis into cells.

Question 15

What happens to chylomicron remnants in the liver?

Answer 15

Degraded by lysosomal enzymes into fatty acids, glycerol, cholesterol, amino acids, and phosphates.

Question 15

How does LCAT function in HDL metabolism?

Answer 15

Converts free cholesterol and phosphatidylcholine into cholesterol esters within HDL particles.

Question 16

What is CETP, and what does it do?

Answer 16

Cholesterol ester transfer protein; transfers cholesterol esters from HDL to VLDL and LDL.

Question 17

A patient presents with milky-white plasma after a fatty meal. What is this called, and what causes it?

Answer 17

Postprandial lipemia due to circulating chylomicrons. Plasma clears as chylomicrons are hydrolyzed (2–2.5 hours).

Question 18

A patient with severe hypertriglyceridemia is found to have a mutation in Apo C-II. Why does this mutation cause elevated triglycerides?

Answer 18

Apo C-II activates lipoprotein lipase (LPL). Loss of function → impaired TAG hydrolysis → accumulation of chylomicrons/VLDL → hypertriglyceridemia.

Question 19

Why is LDL called "bad cholesterol," and what disease is it strongly linked to?

Answer 19

LDL delivers cholesterol to peripheral tissues. High levels → cholesterol deposition in arteries → atherosclerosis.

Question 20

What enzyme esterifies cholesterol in cells to prevent membrane toxicity, and where is it located?

Answer 20

ACAT (Acyl:cholesterol acyltransferase) in the endoplasmic reticulum. Converts free cholesterol → stored esters.

Question 20

Which enzyme converts cholesterol to esters in HDL, and how does this help reverse cholesterol transport?

Answer 20

LCAT (Lecithin:cholesterol acyltransferase). Esterification allows HDL to collect cholesterol from tissues and transport it to the liver.

Question 21

A patient has low HDL. How might this affect other lipoproteins?

Answer 21

HDL donates Apo C-II and Apo E to chylomicrons/VLDL. Low HDL → impaired LPL activation (Apo C-II deficiency) → reduced TAG hydrolysis.

Question 22

How do chylomicrons and VLDL differ in function?

Answer 22

Chylomicrons: Transport dietary (exogenous) TAG. VLDL: Transport liver-synthesized (endogenous) TAG.

Question 23

What happens to chylomicron remnants in the liver, and which apolipoprotein is critical for this process?

Answer 23

Remnants are degraded in lysosomes into cholesterol, fatty acids, etc. ApoE mediates liver uptake via receptors.

Question 24

What is the fate of IDL?

Answer 24

IDL is either (1) taken up by the liver via ApoE or (2) converted to LDL after further TAG removal.

Question 25

How does cholesterol from LDL regulate its own synthesis and uptake in cells?

Answer 25

Inhibits HMG-CoA reductase (blocks synthesis). Downregulates LDL receptors (reduces uptake). Activates ACAT (stores excess as esters).

Question 26

Why do statins (HMG-CoA reductase inhibitors) lower LDL levels?

Answer 26

Reduced cholesterol synthesis → compensatory upregulation of LDL receptors → increased LDL clearance from blood.

Question 27

Which lipoprotein lacks Apo C-II and Apo E after delivering its lipids?

Answer 27

LDL (only has Apo B-100).

Question 28

What role does CETP (cholesterol ester transfer protein) play in HDL metabolism?

Answer 28

Transfers cholesterol esters from HDL to VLDL/LDL in exchange for TAG, reducing HDL’s cholesterol content.

Question 29

Why can’t skeletal muscle store large amounts of TAG compared to adipose tissue?

Answer 29

Muscle lacks enzymes for large-scale TAG storage; TAG is primarily used for energy.

Question 30

What happens to glycerol released during chylomicron/VLDL hydrolysis?

Answer 30

Transported to the liver for gluconeogenesis or glycolysis.

Question 31

Compare HDL and LDL in reverse cholesterol transport.

Answer 31

LDL: Delivers cholesterol to peripheral tissues. HDL: Removes cholesterol from tissues → returns it to the liver.

Question 32

What distinguishes a chylomicron remnant from a mature chylomicron?

Answer 32

Remnants have lost most TAG and Apo C-II but retain Apo B-48 and ApoE for liver uptake.