Cholesterol Metabolism

Question 1

describe the basic chemical features of cholesterol

Answer 1

27 C
4 rings
1 hydrophobic tail
1 hydrophilic OH group**

Question 2

what is the committed step in cholesterol synthesis

Answer 2

production of mevalonate by the enzyme HMG-CoA reductase

Question 3

what inhibits HMG-CoA reductase?

Answer 3

cholesterol: acts on the expression, not at the enzyme level itself

Question 4

what 5 reaction types get mavalonate to farnesyl pyrophosphate?

Answer 4

kinases, decarboxylase, isomerase, transferase, and transferase

Question 5

name the highlighted intermediates from mevalonate to cholesterol

Answer 5

mevalonate –> 5-pyrophosphomevalonate

5-pyrophosphomevalonate —> isopentenyl pyrophosphate (IPP)

isopentenyl pyrophosphate (IPP) —> dimethylallyl pyrophosphate (DPP)

dimethylallyl pyrophosphate (DPP) —> geranyl pyrophosphate (GPP)

geranyl pyrophosphate (GPP) —> farnesyl pyrophosphate (FPP)

farnesyl pyrophosphate (FPP) —> squalene

squalene —> lanosterol

lanosterol –> cholesterol

Question 6

which reactions in cholesterol synthesis need NADPH

Answer 6

FPP —> squalene by squalene synthase uses 1 NADPH

and squalene to lanosterol by squalene monoxygenase uses 1 NADPH

Question 7

which reactions require ATP in cholesterol synthesis

Answer 7

melavonate —> —> 5-pyrophosphomevalonate requires 2 ATP and 5-pyrophosphomevalonate —> isopententyl pyrophosphate (IPP) requires 1 ATP

Question 8

T or F: phosphorylation of HMG CoA reductase is modulated by insulin, glucagon/epinephrine

Answer 8

False

Question 9

is phosphorylated or dephosphorylated HMG CoA reductase active??

Answer 9

dephosphorylated HMG CoA reductase is active

Question 10

describe how HMG CoA reductase is inactivated

Answer 10

-as [AMP] increases, AMP kinase is activated which phosphates HMG CoA reductase rendering it inactive

Question 11

____ dephosphorylates HMG CoA reductase rendering it ____

Answer 11

• phosphoprotein phosphatase

- active

Question 12

T or F: metabolism of cholesterol produces a mass amount of metabolic energy via production of ATP

Answer 12

False. Breakdown of cholesterol does not yield metabolic energy

Question 13

what molecule is converted to bile acids/salts and where does this occur?

Answer 13

cholesterol is converted to bile acids and salts and this occurs in the liver

Question 14

what modification occur in the conversion from cholesterol to bile acids/salts?

Answer 14

27 —> 24 Carbons
additional OH groups added
double bond is eliminated from the B ring

Question 15

Primary bile acids/salts are synthesized in the ___

Secondary bile acids/salts are created in the _____

Answer 15

• primary in the liver

- secondary in the intestine, via bacterial enzymes.

Question 16

amphipathic

Answer 16

having both hydrophilic and hydrophobic parts.

Question 17

amphoteric

Answer 17

able to react both as a base and as an acid.

Question 18

Statins

Answer 18

… a large class of drugs which act as competitive inhibitors
of the regulatory enzyme of cholesterol synthesis.

Question 19

______ a large class of drugs which act as competitive inhibitors of the regulatory enzyme of cholesterol synthesis.

Answer 19

statins

Question 20

Cholesterylamines.

Answer 20

Cholesterol binding resins, that chelate
cholesterol and bile acids/salts in the intestine and are passed in the feces. This forces the recruitment of cholesterol from liver reserves to replenish bile acid/salt stores for future use in digestion/absorption.

Question 21

Ezetimibe.

Answer 21

An inhibitor of dietary cholesterol absorption

-acts on cholesterol transporter

Question 22

statins are structurally similar to what compound?

Answer 22

β-Hydroxy β-methylglutaryl-CoA (HMG-CoA)