Biochem Cholesterol

Question 1

Where is cholesterol synthesized

Answer 1

Liver (50%)

Steroid hormone-producing organs

Question 2

All of the carbon atoms of cholesterol are derived from ___

Answer 2

Acetyl CoA

Question 3

___ catalyze the condensation of 2 acetyl CoA molecules to form one molecule of acetoacetyl CoA.
A third molecule of acetyl CoA is added by ___ to form ___

Answer 3

Cytosolic thiolase
HMG-CoA synthase
3-hydroxy-3-methylglutaryl-CoA

Question 4

HMG-CoA is reduced to ___ by ___

• this enzyme is a major control point for cholesterol synthesis
• it is inhibited by ___

Answer 4

Mevalonate
HMG-CoA reductase
Statins

Question 5

HMG-CoA reductase is embedded in the ___

Answer 5

ER

Question 6

4 steps of the formation of isopentenyl diphosphate (an active isoprenoid unit)

Answer 6

1-3. Sequential phosphorylation by 3 kinases (uses 3 ATP)

4. Decarboxylation

Question 7

Squalene is formed from ____

Steps?

Answer 7

6 isoprenoid units

1. 2 units used to form geranyl diphosphate
2. A third unit is added to form farnesyl diphosphate
3. 2 farnesyl diphosphates are used to synthesize squalene

Question 8

Squalene epoxidase requires _____

___ represents the first sterol produced in the pathway to cholesterol

Answer 8

NADPH and O2

Lanosterol (formed from squalene)

Question 9

There are ___ steps from lanosterol to cholesterol. The process requires what?
It occurs where?

Answer 9

5
4 NADPH and 3 O2
ER

Question 10

The steps from lanosterol and cholesterol involve what?

Answer 10

1. Removal of methyl group at C14
2. Removal of 2 methyl groups at C4
3. Reduction of C24 double bond
4. Moving 8,9 double bind to 5,6

Question 11

Other important products produced from the lanosterol to cholesterol pathway

Answer 11

1. Prenylated proteins
2. Dolichol
3. Ubiquinone

Question 12

Some membrane-associated proteins are prenylated with either ____ or ____ residues, which may anchor the protein to the membrane

Answer 12

Farnesyl or geranylgeranyl

Question 13

Dolichol is formed from ____ and is required for ____

Answer 13

• Farnesyl diphosphate plus up to 16 more isopentenyl residues
• synthesis of N-linked glycoproteins

Question 14

Ubiquinone is formed from ____ and is required for ____

Answer 14

• Farnesyl diphosphate plus 3-7 isopentenyl residues

- electron transport chain

Question 15

ACAT

Answer 15

Acyl CoA cholesterol acyltransferase

*catalyzes lanosterol–>CE

Question 16

Fates of CE?

Uses?

Answer 16

Either packaged into VLDL or stored in the liver for future use
*they are transported to other tissues for steroid hormone synthesis and vitamin D synthesis

Question 17

Bile acids are synthesized in the ___ from ___

Answer 17

Liver

Cholesterol

Question 18

What is the committed step in bile acid synthesis? What does it require?

Answer 18

7 alpha hydroxylase catalyzes rxn from cholesterol to 7 alpha hydroxycholesterol
-requires NADPH, O2, cytochrome P 450, ascorbate (vit C)

Question 19

The liver receives cholesterol from extrahepatic tissues through ___

Answer 19

LDL receptors and reverse cholesterol transport

Question 20

The liver secretes cholesterol into the bloodstream via ___

Answer 20

VLDL

Question 21

3 major regulatory targets in the liver

Answer 21

1. HMG-CoA reductase (cholesterol synthesis)
2. LDL receptor
3. 7alpha-hydroxylase (bile acid synthesis)

Question 22

Binding of ___ to ____ of the HMG-CoA reductase gene stimulates the transcription of the gene.
___ prevents this

Answer 22

SREBP to the SRE
(Sterol regulatory element-binding protein)
-elevated cholesterol levels in the liver

Question 23

SREBP interacts with ___, which contains a sterol binding domain, which does what?

Answer 23

ER membrane protein called SCAP (cleavage activating protein)

• when occupied by cholesterol it keeps the SREBP-SCAP complex in the ER
• when cholesterol levels drop, the cholesterol leaves the SCAP sterol binding site

Question 24

In the ___, SREBP is subjected to proteolysis, and the ___ is released and free to travel to the nucleus Robbins the SRE

Answer 24

Golgi

N-terminal SREBP

Question 25

When sterol sites of HMG-CoA synthase are occupied by cholesterol it is more susceptible to ___

Answer 25

Proteolysis

Question 26

Factors which promote phosphorylation of HMG-CoA reductase (causing inhibition)

Answer 26

1. Glucagon
2. Glucocorticoids
3. Cholesterol

Question 27

Factors which promote dephosphorylation of HMG-CoA reductase (relieving the inhibition)

Answer 27

1. Insulin

2. Thyroid hormone

Question 28

Synthesis of LDL receptors is regulated by ___. The gene is under the same regulatory control as ____

Answer 28

Intracellular cholesterol content

HMG-CoA reductase gene

Question 29

The destruction caused of LDL receptors is promoted by ____, which is secreted by the ___ and binds to ___

Answer 29

PCSK9 (proprotein convertase subtilisin/kexin 9)

• liver
• the LDL receptor at a site other than the LDL binding site

Question 30

When the PCSK9-LDL receptor complex is internalized , the presence of PCSK9 targets ___

Answer 30

The complex to the lysosomes (instead of recycling the receptor)

Question 31

Bile acids bind the ___, which does what?

Answer 31

• FXR (farnesyl X receptor)

- Suppresses the synthesis of 7alpha-hydroxylase (which is the committed step in bile acid synthesis)

Question 32

Equation for LDL cholesterol

Answer 32

Total cholesterol - [HDL + (triglycerides/5)]