Cardiovascular-Renal I: Lipid Metabolism & Cholesterol Hemeostasis (Dr. Chen)

What is the 1st stage of cholesterol biosynthesis?

Acetyl-CoA → HMG-CoA → Mevalonic acid

What is the 2nd stage of cholesterol biosynthesis?

Mevalonic acid → isoprene

What is the 3rd stage of cholesterol biosynthesis?

isoprene → squalene

What is the 4th stage of cholesterol biosynthesis?

squalene → steroid nucleus

What is the rate limiting step in cholesterol biosynthesis?

HMG-CoA → Mevalonic acid

What is the key enzyme/ major regulation point for the rate limiting step of cholesterol biosynthesis?

HMG CoA reductase

What is the function of 7α-hydroxylase?

convert cholesterol to cholic acid which becomes bile acid/salts in liver

What are the 3 steps of lipid digestion?

1. emulsification (bile salts)

2. hydrolysis of TGs (lipase)

3. micelles (dissolving of FA & monoglyceride)

What are the 4 steps of cholesterol absoption?

1. De-esterified by esterases (via ester hydrolysis)

2. Taken up by the cholesterol transporter (NPC1L1)

3. Re-esterified to cholesterol esters by sterol-o-acyltransferase

4. incorporated into chylomicrons

Which of the following statements about circulating lipoproteins is correct?

A. Lipoproteins have the same apoproteins attached to their outer surface.

B. LDL primarily functions in transporting cholesterol to peripheral tissues.

C. HDL contains mostly triglycerides in its core.

D. VLDL primarily functions in transporting cholesterol to peripheral tissues.

B

Which of the following would be a consequence of inhibiting the binding of LDL to its receptor?

A. There would be a decrease in the production of chylomicrons.

B. There would be an increase in cholesterol levels in serum.

C. There would be a decrease in the production of HDL levels.

D. There would be an increase in intestinal absorption of triglycerides.

B

HDL is a type of lipoprotein that is important for acquiring cholesterol from VLDL and chylomicrons. Which of the following proteins are important for HDL function?

A. Apo A-I

B. Lecithin-Cholesterol Acyltransferase (LCAT)

C. Cholesteryl Ester Transport Protein

D. All of the Above

A

Which of the following PPARs can decrease the circulating LDL level?

A.PPARβ

B.PPARδ

C.PPARα

D.PPARγ

C

What is the primary function of chylomicrons?

transport dietary lipids

What is the primary function of VLDLs?

transport endogenous TGs

What is the primary function of LDLs?

transport cholesterol

What is the primary function of Apo B-100?

receptor binding

Where are LDLRs found?

in plasma membrane located at clathrin-coated pits

What is the function of LDLR?

remove circulating LDLs & transport them into cells to regulate cholesterol levels

What is the function of PCSK9 proteins?

bind to LDLRs to promote LDLR degradation

What is the function of ApoB-100?

structure protein for VLDL, IDL and LDL; ligand for LDLR

What is the function of ApoA-1?

structure protein for HDL, CM; activator of LCAT

What is LCAT? lecithin-cholesterol acyltransferase

catalyze the esterification of free cholesterol to make mature HDLs (HDL3)

important for RCT

Binds to LDLs & HDLs

How is LCAT activated?

by ApoAI on HDL surface

What is RCT? Reverse Cholesterol Transport

excess cholesterol in peripheral cells (esp foam cells) return to liver for degradation & excretion