Lipids and Lipoproteins - Cholesterol

Question 1

Where is Acetyl CoA generated?

Answer 1

Mitochondria

Question 2

How many Acetyl CoA are necessary to form 1 IPP (Isopentenyl Pyrophosphate)?

Answer 2

3

Question 3

What are Isopentenyl Pyrophosphates the building blocks for?

Answer 3

Isoprenoids

Question 4

What are 3 types of Isoprenoids?

Answer 4

1. Steroids - ex. Cholesterol
2. Fat soluble vitamins (ADEK)
3. ubiquinone

Question 5

How many carbons make up IPP?

Answer 5

5

Question 6

How many carbons are in 1 Acetyl CoA?

Answer 6

2

Question 7

How many units of IPP are needed to make a sterane (4-ring) ring?

Answer 7

6

Question 8

Cholesterol is made of what type of ring?

Answer 8

Sterane (4-ring)

– From 6 units of IPP

Question 9

What are the major physical features of cholesterol molecules?

Answer 9

Sterane ring with 27 carbons

Hydroxyl group on the 3rd carbon

Question 10

Are cells able to degrade cholesterol?

Answer 10

NO - must be used or excreted by the liver

Question 11

Biosynthesis of cholesterol is ______ proportional to the dietary intake of cholesterol

Answer 11

INVERSELY = the more cholesterol you eat the less you will make in your body

Question 12

What is the overall reaction to make Cholesterol?

Answer 12

18 Acetyl CoA + 18 ATP + 16 NADPH = Cholesterol

Question 13

What is the order of which products are made in phase 1 of cholesterol synthesis?

Answer 13

Acetyl CoA
Acetoacetyl CoA
HMG CoA
Mevalonate
Isopentenyl Pyrophosphate (IPP)

Question 14

What enzyme takes Acetoacetyl CoA to HMG CoA?

Answer 14

HMG CoA Synthase

Question 15

HMG CoA

Answer 15

Hydroxymethylglutaryl CoA

Question 16

What enzyme takes HMG CoA to Mevalonate?

Answer 16

HMG CoA Reductase

Question 17

What is the rate-limiting step of cholesterol synthesis?

Answer 17

HMG CoA (using HMG CoA Reductase and NADPH) goes to Mevalonate in phase 1

Question 18

What is the order of which products are made in phase 2 of cholesterol synthesis?

Answer 18

6 Isopentenyl Pyrophosphates (IPPs)
Squalene
Lanosterol
Cholesterol

Question 19

Once cholesterol is formed, what are its 2 options?

Answer 19

1. Form Cholesterol Esters

2. Packaged into VLDL and sent into blood

Question 20

What do Statin drugs do?

Answer 20

LOWER cholesterol

Question 21

Where do Statin drugs work?

Answer 21

They INHIBIT HMG CoA Reductase enzyme (rate-limiting step)

Question 22

Good side effect of Statin drugs?

Answer 22

Help to clear cholesterol via LDL receptor mediated endocytosis

Question 23

Bad side effect of Statin drugs?

Answer 23

Deplete muscle levels of ubiquinone

– due to acting on pathway before IPP is generated!!

Question 24

Where is cholesterol synthesis regulated?

Answer 24

HMG CoA Reductase enzyme

Question 25

What can directly inhibit HMG CoA Reductase enzyme and thus, cholesterol formation?

Answer 25

- Bile acids - Statins - Free fatty acids

Question 26

If HMG CoA Reductase enzyme is phosphorylated it is _____

Answer 26

INactive

Question 27

If HMG CoA Reductase enzyme is DEphosphorylated it is _____

Answer 27

ACTIVE

Question 28

What states or molecules want HMG CoA Reductase to be phosphorylated?

Answer 28

(INACTIVE) | Low energy states and Glucagon

Question 29

What states or molecules want HMG CoA Reductase to be dephosphorylated?

Answer 29

(ACTIVE) | Insulin

Question 30

Another way to regulate cholesterol synthesis is through transcriptional control. What protein is involved?

Answer 30

SREBP

Question 31

SREBP binds SCAP to form a complex in the ER. What will stimulate that complex to be moved to the Golgi?

Answer 31

LOW cholesterol levels

Question 32

Once the SREBP-SCAP complex is in the Golgi, what is formed and through what mechanism?

Answer 32

Mature SREBP through cleavage

Question 33

What does mature SREBP bind?

Answer 33

SRE in the nucleus

Question 34

Overall effect of mature SREBP binding to SRE in the nucleus?

Answer 34

INCREASED transcription of HMG CoA Reductase

Question 35

SREBP

Answer 35

Sterol Regulatory Element Binding Protein

Question 36

SCAP

Answer 36

SREBP - Cleavage Activating Protein

Question 37

SRE

Answer 37

Sterol Regulatory Element

Question 38

If there is increased transcription of HMG CoA Reductase, what does that cause?

Answer 38

- Increase in cholesterol formation | - Upregulation of LDL receptor

Question 39

What will cause the SREBP-SCAP complex to be retained in the ER?

Answer 39

HIGH cholesterol levels -- do not need to make more