Cholesterol Metabolism and Biosynthesis

Question 1

What are the primary roles of cholesterol in the body?

Answer 1

Component of cell membranes
Precursor of steroid hormones
Bile acids
Vitamin D

Question 2

What condition is associated with high blood cholesterol levels?

Answer 2

Cardiovascular disease

Question 3

What cholesterol level is considers high risk by AHA?

Answer 3

> 200 mg/dL total blood cholesterol

Question 4

How many Americans over the age of 10 have >200 mg/dL cholesterol?

Answer 4

Around 100 million

Question 5

What is the carbon source for cholesterol biosynthesis?

Answer 5

Acetate

Question 6

What intermediates are used in cholesterol biosynthesis?

Answer 6

Isoprene units

Question 7

Where does cholesterol synthesis primarily occur?

Answer 7

Liver

Question 8

What happens in stage 1 of cholesterol biosytnthesis?

Answer 8

Acetyl-CoA –> HMG-CoA –> Mevalonate via HMG-CoA Reductase

Question 9

What happens in stage 2 of cholesterol biosytnthesis?

Answer 9

Mevaonate –> Isopentenyl pyrophosphate via ATP and decarboxylation

Question 10

What happens in stage 3 of cholesterol biosytnthesis?

Answer 10

Six isoprenes –> Squalene via farnesyl pyrophpshates

Question 11

What happens in stage 4 of cholesterol biosytnthesis?

Answer 11

Squalene –> Lanosterol –> Cholesterol (20+reactions)

Question 12

In what forms is cholesterol exported from the liver?

Answer 12

Biliary cholesterol
Bile acids
Cholesteryl esters

Question 13

What is the role of esterification in cholesterol transport?

Answer 13

Increases hydrophobicity for storage and transport

Question 14

What are the end uses of cholesterol?

Answer 14

Membranes
Steroid hormones
Vitamin D

Question 15

How is cholesterol transorted in blood?

Answer 15

Via lipoproteins (LDL, HDL, etc)

Question 16

What does LDL contain?

Answer 16

1,500 cholesteryl esters
500 cholesterol
ApoB-100

Question 17

How does LDL deliver cholesterol to cells?

Answer 17

LDL receptor binds ApoB-100 –> uptake –> hydrolysis in lysosome

Question 18

How doe HDL collect cholesterol?

Answer 18

ABC transporters send cholesterol to ApoA-1 in HDL –> LCAT esterifies it –> HDL returns to liver

Question 19

What is the relationship between HDL and heart disease?

Answer 19

Inverse correlation
Higher HDL = lower arterial disease risk

Question 20

What is the master regulator enzyme in cholesterol biosynthesis?

Answer 20

HMG-CoA Reductase

Question 21

What transcription factors regulate cholesterol synthesis?

Answer 21

SREBPs
(Sterol Regulatory Element Binding Proteins)

Question 22

How are SREBPs activated?

Answer 22

When cholesterol is low, they are cleaved and enter the nucleus

Question 23

What hormones regulate HMG-CoA Reductase?

Answer 23

Insulin (activates by dephosphorylation)
Glucagon (inhibits by phosphorylation)

Question 24

What is the effect of high cholesterol on LDL receptor expression?

Answer 24

Decreases LDL receptor gene transcription

Question 25

What is Familial Hypercholesterolemia?

Answer 25

Defected LDL receptor means high cholesterol and leads to early-onset atherosclerosis

Question 26

What causes Familial HDL Deficiency and Tangier Disease?

Answer 26

Defective ABC-1 transporter means HDL cannot pick up cholesterol leads to low HDL and increased CVD risk

Question 27

What are consequences of unregulated cholesterol production?

Answer 27

Atherosclerosis due to plaque buildup

Question 28

What are satins and how do they work?

Answer 28

Competitive inhibitors of HMG-CoA Reductase Mimic mevvalonate to block cholesterol synthesis