Blomquist: Cholesterol

Question 1

Role of cholesterol

Answer 1

membranes
precursor to bile salts/acids
precursor to hormones
precursor to vitamin D

Question 2

This makes up greater than 80% of gall stones

Answer 2

cholesterol

Question 3

How many carbons does cholesterol have? How many rings does cholesterol have? At what position is the hydroxyl group? At what positions are there methyl groups? At what position is there a double bond? How long is the carbon side chain?

Answer 3

27; four; 3; 18, 19; C5-C6; 8 carbons

Question 4

Where is most of the cholesterol found in the human body?

Answer 4

In membranes

Question 5

What is the concentration of cholesterol in the blood?

Answer 5

150-240mg/dL

Question 6

In what form is most of the cholesterol carried in the blood?

Answer 6

As a cholesterol ester; lipoprotein

Question 7

Is cholesterol polar or non-polar?

Answer 7

non-polar

Question 8

Acetyl-CoA is required for cholesterol synthesis. What are two source of Acetyl-CoA?

Answer 8

carbohydrates or fatty acids

Question 9

What is the regulated enzyme in cholesterol biosynthesis?

Answer 9

HMG-CoA reductase

Question 10

HMG-CoA reductase takes Acetyl-CoA to what intermediate?

Answer 10

mevalonate

Question 11

What two things combine to make HMG-CoA via HMG-CoA synthase?

Answer 11

acetoacetyl-CoA + acetyl-CoA

Question 12

In the cytosol, what does HMG-CoA go to?

In the mito matrix, what does HMG-CoA go to?

Answer 12

cholesterol; ketone bodies

Question 13

What does the HMG-CoA reductase reaction require?

Answer 13

2NADPH being reduced to 2NADP+

Question 14

What is the complete equation for the formation of mevalonate from HMG-CoA?

Answer 14

HMG-CoA + 2NADPH + 2H+ –> mevalonate + 2NADP+ + CoA

Question 15

In what ways is HMG-CoA regulated?

Answer 15

feedback inhibition
phosphorylation/dephosphorylation
control of gene expression
rate of enzyme degradation

Question 16

Discuss the feedback inhibition of the cholesterol pathway.

Answer 16

If there is lots of cholesterol already in the body, this will inhibit HMG-CoA reductase

Question 17

Phosphorylation is another method of control of HMG-CoA reductase. When HMG-CoA reductase is phosphorylated, is it active or inactive?

Answer 17

inactive

Question 18

HMG-CoA reductase is also controlled at the gene level. The sterol receptor element binding protein can bind to the (blank) and increase (blank) of target genes, which increases the synthesis of (blank).

Answer 18

nucleus; transcription; HMG-CoA reductase

Question 19

Because of its structural similarities to HMG-CoA, this can be used as a competitive inhibitor of HMG-CoA reductase

Answer 19

Lipitor; Lovastatin

Question 20

What is a potential problem when using statins?

Answer 20

The cholesterol pathway produces intermediates that are essential to formation of prenylated proteins, vitamin D, bile salts, and steroids. So, when you block HMG-CoA reductase, you block the pathways for these other products as well.

Question 21

Through what carbon intermediates does mevalonate pass through to make cholesterol (C27)?

Answer 21

C5, C10, C15, C30

Question 22

19 oxidation steps take lanosterol to cholesterol. What do these steps require?

Answer 22

Cytochrome P450s

Question 23

Where are bile salts made from cholesterol?

Answer 23

in the liver

Question 24

Where are bile salts stored?

Answer 24

gall bladder

Question 25

Where are bile salts transported after leaving the liver?

Answer 25

small intestine

Question 26

Cholesterol is present in bile acids in small amounts and can form these

Answer 26

gall stones

Question 27

If the gall bladder is removed, bile acids go directly to the (blank)

Answer 27

small intestine

Question 28

What is the purpose of converting cholesterol to bile acids/salts?

Answer 28

to emulsify fats

Question 29

What gets conjugated to bile acids/salts to make then better solubilizing agents?

Answer 29

Glycine, Taurine

Question 30

How do conjugated bile acids/salts aid in the processes of the duodenum? (think pKa)

Answer 30

These conjugates have Pkas of 1-4, and the duodenum is 3-5

Question 31

This compound binds to bile salts and removes them from the body, forcing more cholesterol to be converted to bile salts. This is one way to reduce cholesterol.

Answer 31

cholestyramine

Question 32

What is unique about cholestyramine that allows it to bind bile salts and remove them from the body?

Answer 32

N+ which binds negatively charged bile acids

Question 33

How much of bile salts are typically reabsorbed?

Answer 33

90%

Question 34

How does acetyl-CoA get out of the mito matrix and into the cytosol?

Answer 34

pyruvate shuttled through inner mito membrane after glycolysis pyruvate --> OAA OAA + acetyl-CoA in matrix converted to citrate citrate transported through the membrane citrate converted back to OAA, liberating acetyl-CoA in the cytosol then, OAA --> malate --> pyruvate to do it all again!

Question 35

``` prenylated proteins heme a dolichol ubiquinone vit D squalene ```

Answer 35

Products formed in the process of making cholesterol from HMG-CoA

Question 36

Binding of bile salts to cholestyramine is what type of interaction?

Answer 36

ionic bonding