Lecture 13 (Part 5) - Proprotein Convertase Subtilisin/Kexin 9 (PCSK9)

Question 1

What is the primary source of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) in the body?

Answer 1

PCSK9 is primarily secreted from the liver.

Question 2

How does PCSK9 affect the function of LDL receptors on hepatocytes?

Answer 2

PCSK9 binds to the LDL receptor on the surface of hepatocytes, leading to the intracellular degradation of the LDL receptor in the lysosomes of hepatocytes.

Question 3

What effect does PCSK9 have on the cholesterol contents of LDL particles?

Answer 3

PCSK9 prevents LDL from emptying its cholesterol contents into the liver, particularly when there is already a sufficient amount of cholesterol present in the liver.

Question 4

How does PCSK9 influence the regulation of LDL uptake in the body?

Answer 4

PCSK9 regulates LDL uptake by modulating the activity of LDL receptors on hepatocytes.

Question 5

What benefit does inhibition of PCSK9 offer in managing cholesterol levels?

Answer 5

Inhibition of PCSK9 offers a novel therapeutic mechanism for lowering LDL cholesterol levels in the circulation, as it allows for more LDL uptake by the liver.

Question 6

What factor inhibits PCSK9 if present in sufficient amounts in the liver?

Answer 6

Sufficient bile in the liver inhibits PCSK9.

Question 7

How does the inhibition of PCSK9 contribute to reducing LDL cholesterol levels?

Answer 7

Inhibition of PCSK9 prevents it from binding to the LDL receptor, allowing LDL to be continuously taken up by the liver, resulting in less LDL remaining in circulation.

Question 8

Describe a potential approach to target PCSK9 for therapeutic purposes.

Answer 8

One potential approach involves developing a drug that binds to PCSK9 while it is in circulation, preventing it from binding to the LDL receptor. This allows LDL to continue being taken up by the liver, reducing its levels in circulation.