CPPS303 XIAO Lecture 4 Liver Lipid 2 March_17_2025 (1)

Question 1

What are the main components of chylomicrons?

Answer 1

TAG, phospholipids, cholesterol, and apolipoproteins

Question 2

Where are chylomicrons synthesized?

Answer 2

In the intestine

Question 3

What enzyme partially hydrolyzes chylomicron TAG?

Answer 3

Lipoprotein lipase (LPL)

Question 4

What products result from the hydrolysis of chylomicron TAG?

Answer 4

Glycerol, fatty acids, and chylomicron remnants

Question 5

What is the role of chylomicron remnants after they are transported to the liver?

Answer 5

They enter hepatocytes by receptor-mediated endocytosis

Question 6

Which receptors are involved in the uptake of chylomicron remnants?

Answer 6

Heparan sulfate proteoglycans (HSPG) and low-density lipoprotein receptor (LDLR)

Question 7

What is the half-life of LDL in the plasma?

Answer 7

2-3 days

Question 8

What percentage of LDLs does the liver degrade?

Answer 8

~40-60%

Question 9

What is the major function of LDL in the body?

Answer 9

Carriers of cholesterol in plasma

Question 10

What transporter facilitates the efflux of cholesterol in peripheral cells?

Answer 10

ABCA1

Question 11

What enzyme esterifies cholesterol to form cholesteryl ester (CE)?

Answer 11

Lecithin–cholesterol acyltransferase (LCAT)

Question 12

What is the function of cholesteryl ester transfer protein (CETP)?

Answer 12

Mediates lipid transfer between VLDL/IDL/LDL and HDL

Question 13

What is the rate-limiting step in cholesterol synthesis?

Answer 13

HMG-CoA reductase

Question 14

What class of drugs are HMG-CoA reductase inhibitors?

Answer 14

Statins

Question 15

What are the major pools of cholesterol in the body?

Answer 15

• Cholesterol and cholesterol derivatives in bile
• Cholesterol in membranes
• Cholesterol carried as lipoproteins in blood
• Cholesterol-rich tissues (e.g., adipose tissue)

Question 16

What is the most important route for cholesterol elimination in mammals?

Answer 16

Hepatic conversion of cholesterol into bile acids

Question 17

What is reverse cholesterol transport (RCT)?

Answer 17

A mechanism by which the body removes excess cholesterol from peripheral tissues and delivers it to the liver

Question 18

What receptors mediate the selective uptake of HDL-CE in the liver?

Answer 18

Scavenger receptor class B type 1 (SR-B1)

Question 19

What happens to LDL particles after they bind to LDLR?

Answer 19

They are internalized and degraded in the lysosome

Question 20

What is the role of PCSK9 in cholesterol homeostasis?

Answer 20

Regulates LDL receptor degradation

Question 21

What tissues express PCSK9?

Answer 21

• Liver
• Intestine
• Kidney
• Skin
• Central nervous system

Question 22

What regulates the expression of PCSK9?

Answer 22

SREBP-1/2

Question 23

Fill in the blank: The liver synthesizes cholesterol primarily from _______.

Answer 23

[de novo synthesis and dietary uptake]

Question 24

What regulates expression in the kidney, skin, and central nervous system?

Answer 24

SREBP-1/2

Question 25

What is the crucial protein in LDL metabolism?

Answer 25

PCSK9

Question 26

What does PCSK9 regulate?

Answer 26

LDL receptor degradation

Question 27

What complex is internalized into hepatocytes for lysosomal degradation?

Answer 27

LDL, LDLR, and PCSK9

Question 28

What is the outcome of LDLR not recycling back to the cell surface?

Answer 28

Increases LDL level, leading to CVD

Question 29

What human mutations are linked to circulating cholesterol levels and CVD risks?

Answer 29

Gain-of-function: high cholesterol; Loss-of-function: low cholesterol

Question 30

What is the effect of PCSK9 inhibition?

Answer 30

Lowers LDL

Question 31

What do monoclonal antibodies bound to PCSK9 do?

Answer 31

Prevent the association between PCSK9 and LDLR

Question 32

Name a method of gene silencing.

Answer 32

Small interference RNA (siRNA), antisense oligonucleotide (ASO), epigenetic modification

Question 33

What are other therapeutic approaches to lower LDL?

Answer 33

Small molecule inhibitors

Question 34

What is involved in intravascular lipolysis and remodeling of lipoproteins?

Answer 34

Cholesterol metabolism in the liver

Question 35

What are the sources of cholesterol?

Answer 35

Liver and dietary intake

Question 36

What role does HDL play in cholesterol transport?

Answer 36

Selective uptake of cholesterol, reverse cholesterol transport, CE-TG lipid transfer

Question 37

What are the components involved in reverse cholesterol transport?

Answer 37

LDL receptor and PCSK9