Cholesterol Metabolism

Question 1

What are the four primary functions of cholesterol?

Answer 1

• Affects cell membrane fluidity
• Precursor of bile acids/salts
• Precursor of steroids
• Precursor of vitamin D

Question 2

What are the three major sources of liver cholesterol?

Answer 2

• Dietary cholesterol
• De Novo synthesis in the liver
• De Novo synthesis in non-liver locations

Question 3

What transports dietary cholesterol to the liver? What transports cholesterol from non-liver tissues to the liver?

Answer 3

• Dietary cholesterol is transported via CM remnants

- Cholesterol from non-hepatic tissues is transported via HDL

Question 4

What are the three major routes by which cholesterol leaves the liver?

Answer 4

• Free cholesterol
• As bile acids/salts
• As components of VLDL

Question 5

What part of the cell does De Novo cholesterol synthesis occur? In what type of tissue cells?

Answer 5

De Novo cholesterol synthesis occurs in the cytosol of all tissues, especially the liver (cholesterol is needed to decrease membrane fluidity)

Question 6

When does De Novo cholesterol synthesis occur and under what conditions?

Answer 6

De Novo cholesterol synthesis occurs during fed state when ATP and NADPH levels are high

Question 7

What is the starting substrate and product of the first step of De Novo cholesterol synthesis? What enzyme is used?

Answer 7

Acetyl CoA > HMG CoA via HMG CoA Synthase(cyto)

Question 8

What part of the cell is the HMG CoA Synthase used in De Novo cholesterol synthesis found? Which process is the other HMG CoA Synthase used in?

Answer 8

HMG CoA Synthase(cyto) is used in De Novo cholesterol synthesis

• HMG CoA Synthase(mito) is used in Ketogenesis

Question 9

What is the starting substrate and product of the second step of De Novo cholesterol synthesis? What enzyme is used?

Answer 9

HMG CoA > Mevalonic Acid via HMG CoA Reductase

Question 10

What is the starting substrate and product of the third step of De Novo cholesterol synthesis?

Answer 10

Mevalonic Acid > Cholesterol

Question 11

What is the rate limiting enzyme of De Novo cholesterol synthesis?

Answer 11

HMG CoA Reductase is the rate limiting enzyme (second step)

Question 12

What are the two energy carriers utilized in De Novo cholesterol synthesis?

Answer 12

NADPH and ATP

Question 13

What is the name of the enzyme that produces cholesterol esters (CEs) from cholesterol? What activates this enzyme?

Answer 13

Cholesterol > CE via ACAT

ACAT is activated by high cytosolic cholesterol

Question 14

What are the two possible fates of CEs created in the liver by ACAT?

Answer 14

• Packaged into VLDLs and exported to the blood

- Stored in the liver as lipids droplets

Question 15

What are the three major regulatory mechanisms used by cells to regulate cytosolic cholesterol levels?

Answer 15

• De Novo cholesterol synthesis (gene expression of HMG CoA Reductase)
• LDL endocytosis/synthesis of LDL receptors
• Storage via ACAT activity

Question 16

If cytosolic cholesterol levels are elevated, how will gene expression of HMG CoA Reductase be affected?

Answer 16

Expression of HMG CoA Reductase will be decreased to lower the cellular production of new cholesterol (De Novo)

Question 17

If cytosolic cholesterol levels are elevated, how will synthesis of LDL receptors be affected?

Answer 17

LDL receptor synthesis will be decreased to lower the import of cholesterol from the blood

Question 18

If cytosolic cholesterol levels are elevated, how will ACAT activity be affected?

Answer 18

ACAT activity will be increased in order to store cholesterol

Question 19

What are the two ways to get rid of cholesterol?

Answer 19

• Convert cholesterol to bile acids then bile salts

- Secrete cholesterol into the bile (eliminated in feces)

Question 20

What are the two possible fates of bile acids/salts?

Answer 20

• Go directly from liver into duodenum through the common bile duct (enterohepatic circulation)
• Stored in the gallbladder for future use

Question 21

What is the name of the enzyme that produces bile acids from cholesterol? What activates and inhibits this enzyme? What is the only tissue cell type where this enzyme is found?

Answer 21

Cholesterol > Bile acids via Cholesterol 7-alpha-hydroxylase

Cholesterol 7-alpha-hydroxylase is activated by cholesterol (starting substrate) and inhibited by bile salts (product)

Cholesterol 7-alpha-hydroxylase is only found in the liver

Question 22

What are the two most common primary bile acids?

Answer 22

• Cholic acid

- Chenodeoxycholic acid

Question 23

Which two amino acids are added to bile acids to create bile salts?

Answer 23

Taurine and Glycine

Question 24

What are the four most common primary bile salts?

Answer 24

• Glycocholic acid
• Glycochenodeoxycholic acid
• Taurocholic acid
• Taurochenodeoxycholic acid

Question 25

What is the hydrophobicity scale?

Answer 25

Bile salts < Bile acids < Cholesterol < CEs

Question 26

What two actions can intestinal bacteria perform on bile acids/salts?

Answer 26

• Deconjugate bile salts (remove the taurine or glycine)

- Dehydroxylate bile acids

Question 27

What is a secondary bile acid/salt? What are the two most common secondary bile acids?

Answer 27

A secondary bile acid/salt lacks a hydroxyl group at position 7

The two most common secondary bile acids are deoxycholic acid and lithocholic acid

Question 28

Where can secondary bile acids be reconjugated? Can they be rehydroxylated?

Answer 28

Secondary bile acids are reconjugated (taurine or glycine re-added) in the liver

They CANNOT be rehydroxylated

Question 29

What is enterohepatic circulation? Describe this process.

Answer 29

Enterohepatic circulation is the continuous flow of bile salts

Starts in the liver > passage through the duodenum (some are converted back to bile acids via deconjugation and dehydroxylation by intestinal bacteria) > return to the liver as a mixture of bile acids/salts