Cholesterol OBJ Flashcards

1
Q

Thiolase 1 (3-ketacyl-CoA) uses which pathway?
a.) Degrative Pathways
B. Condensation Pathway
C. Biosynthetic Pathway
D. Pericardium Pathway

A

a.) Degrative Pathways

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2
Q

What is the size of Thiolase l?
A. 2 Amino acids
B. 3-4 Carbon atoms
C. 4-22 Carbon Atoms
D. 25 Amino acids

A

C. 4-22 Carbon Atoms

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3
Q

The crystal structure of the biosynthetic thiolase tetramer is in close resemblance to which of
the following crystal structure?
A. HMG-CoA
B. Yeast Degrative Thiolase
C. Mevalonic Acid
D. Dimethylallyl-PP

A

B. Yeast Degrative Thiolase

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4
Q

For HMG-CoA Synthase, what molecule is not involved in the mechanism to form
HMG-CoA?
A. Water
B. Acetyl-CoA
C. Acetoacetyl-CoA
D. CO2

A

D. CO2

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5
Q

For HMG-CoA Synthase, what amino acid residue in the active site binds to the substrate?
A. Cysteine
B. Histidine
C. Glutamate
D. Lysine

A

A. Cysteine

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6
Q

For HMG-CoA Synthase, what is the correct order of events for the mechanism?
A. Condensation, Hydrolysis, Deacetylation
B. Deacetylation, Condensation, Hydrolysis
C. Hydrolysis, Condensation, Deacetylation
D. Deacetylation, Hydrolysis, Condensation

A

B. Deacetylation, Condensation, Hydrolysis

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7
Q

How many NADPH are required in the reduction of the mevalonate pathway?
a. 1
b. 2
c. 3
d. 0

A

b. 2

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8
Q

What is the significance of this 3rd step in cholesterol synthesis?
a. It is the rate limiting step
b. It is unfavorable and thus requires ATP
c. It produces Acetyl-CoA
d. None of the above

A

a. It is the rate limiting step

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9
Q

What is a key component of HMG-CoA reductases crystal structure?
a. Trans-loop
b. Cis-loop
c. The 4th domain
d. The H-bonds between residues

A

b. Cis-loop

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10
Q

What is the protein size of Mevalonate kinase?
a) 32 kDa
b) 45 kDa
c) 64 kDa
d) 728 kDa

A

a) 32 kDa

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11
Q

Which best describes the favorability of mevalonic acid -> mevalonate-5-phosphate?
a) Favorable; paired with hydrolysis of ATP.
b) Unfavorable; paired with hydrolysis of ATP.
c) Favorable; not paired with another reaction.
d) Unfavorable; not paired with another reaction.

A

b) Unfavorable; paired with hydrolysis of ATP.

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12
Q

What are the required cofactors needed for mevalonic acid -> mevalonate-5-phosphate?
a) ATP
b) Mg 2+
c) NAD+
d) Both ATP and Mg 2+

A

d) Both ATP and Mg 2+

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13
Q

What type of reaction is reaction 5 in cholesterol synthesis?
a. Ordered
b. First ordered
c. Second ordered
d. Sequential

A

d. Sequential

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14
Q

What is the class of protein in reaction 5 of cholesterol synthesis?
a. Nucleoside monophosphate kinase
b. Nucleoside diphosphate kinase
c. Oxidoreductase
d. Extracellular matrix protein

A

a. Nucleoside monophosphate kinase

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15
Q

What enzyme catalyzes the reaction of mevalonate-5-phosphate to mevalonate-5-
pyrophosphate?
a. HMG-CoA reductase
b. Phosphomevalonate kinase
c. HMG-CoA synthase
d. Thiolase

A

b. Phosphomevalonate kinase

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16
Q

The reaction of Mevalonate-5-pyrophosphate to Isopetenyl-5-pyrophosphate is
A. favorable endothermic
B. not favorable and endothermic
C. favorable and exothermic
D. not favorable and exothermic

A

B. not favorable and endothermic

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17
Q

What family does mevalonate-5-pyrophosphate decarboxylase belongs to?
a) CDC7 family
b) Haspin family
c) IKK family
d) GHMP kinase family

A

d) GHMP kinase family

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18
Q

What enzyme catalyzes the reaction of Mevalonate-5-pyrophosphate to Isopenty-5- pyrophosphate?
a) Mevalonate-5-pyrophosphate decarboxylase
b) Mevalonate kinase
c) Isopentyl-PP-isomerase
d) Phosphomevalonate kinase

A

a) Mevalonate-5-pyrophosphate decarboxylase

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19
Q

What class is the enzyme in the transformation of IPP to DMAPP (step 7)?
A. Isomerase
B.Sequential
C. Transferase
D. Hydrolase

A

A. Isomerase

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20
Q

Which two amino acids make up the active site for IPP Isomerase?
A. Cysteine and Arginine
B. Glutamic Acid and Aspartic Acid
C. Glutamic Acid and Cysteine
D. Threonine and Cysteine

A

C. Glutamic Acid and Cysteine

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21
Q

Where in the cell does step 7 of cholesterol synthesis occur?
A. Golgi Apparatus
B. Nucleolus
C. Cytoplasm
D. Endoplasmic Reticulum

A

D. Endoplasmic Reticulum

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22
Q

What type of reaction is step 8 of cholesterol synthesis pathway?
a. Nucleophilic substitution reaction
b. Sequential reaction
c. Hydrolysis reaction
d. Oxidation/ Reduction Reaction

A

b. Sequential reaction

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23
Q

What does Farnesyl Phosphate Synthase do in the conversion of IPP to DMAPP?
a. It catalyzes the head- to tail condensation reaction
b. It converts the entire reaction into a Redox reaction
c. It catalyzes the reaction in the reverse direction
d. It makes the carbons more sterically hindered therefore having less stability

A

a. It catalyzes the head- to tail condensation reaction

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24
Q

What is/are the products of step 8 of the cholesterol synthesis pathway?
a. ATP
b. Hexokinase
c. Geranyl Phosphate
d. Hydrochloric acid and Water

A

c. Geranyl Phosphate

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25
Q

Which is the most important motif for catalytic activity in step 9?
a. Glutamate-rich
b. Aspartate-rich
c. Lysine-rich
d. Serine-rich

A

b. Aspartate-rich

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26
Q

Which is a catalytic mechanism proposed for step 9?
a. Condensation initiated by heterolytic cleavage of C-O bond, yielding a carbocation
intermediate
b. Condensation initiated by homolytic cleavage of C-O bond, yielding a carbocation
intermediate
c. Formation of C2-C5 bond between substrates and simultaneous rupture of C1-O bond
through a transition state with carbocation character
d. None of the above

A

a. Condensation initiated by heterolytic cleavage of C-O bond, yielding a carbocation
intermediate

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27
Q

What kind of inhibition can occur in step 9?
a. Competitive
b. Uncompetitive
c. Allosteric (noncompetitive)
d. No inhibition occurs

A

c. Allosteric (noncompetitive)

28
Q

What type of enzyme is squalene synthase?
A) Transferase
B) Isomerase
C) Amylase
D) Cellulase

A

A) Transferase

29
Q

Which step in the pathway is the first committed step in cholesterol synthesis?
A) 1
B) 4
C) 10
D) 7

A

C) 10

30
Q

What cofactors are needed for the synthesis of farnesyl pyrophosphate to squalene?
A) Mg2+
B) NADPH
C) FADPH
D) Mg2+ and NADPH

A

D) Mg2+ and NADPH

31
Q

What organelle does Squalene Monooxygenase embed itself in?
a. Mitochondria
b. Nucleus
c. Endoplasmic Reticulum
d. Cytoplasmic Membrane

A

c. Endoplasmic Reticulum

32
Q

What type of enzyme is Squalene Epoxidase?
a. Oxidoreductase
b. Hydrolase
c. Lyase
d. DNA polymearse

A

a. Oxidoreductase

33
Q

Is the reaction of Squalene to 2-3 oxidosqualene favorable??
a. Yes
b. No
c. I don’t know

A

a. Yes

34
Q

What class of enzyme is used in Lanosterol synthesis?
A) Reductase
B) Transferase
C) Isomerase
D) Amylase

A

C) Isomerase

35
Q

What domains is the enzyme composed of?
A) 3 Beta Pleated Sheets
B) 2 Parallel Twisted Sheets
C) 4 Alpha-Beta Barrels
D) 2 Alpha-Helix Barrels

A

D) 2 Alpha-Helix Barrels

36
Q

What amino acid residue is used to protonate 2,3-oxidosqualene?
A)Tyr 503
B)Asp 455
C)Lys 237
D)Glu 394

A

B)Asp 455

37
Q

What is the total amount of cofactors needed for this reaction?
a. O 2 +NADPH
b. 3x (H2O +NADPH)
c. 3x (NADPH + H + O 2)
d. 2x (H2O + NADPH)

A

c. 3x (NADPH + H + O 2)

38
Q
  1. What is the name of the enzyme for step 13?
    a. 14α-demethylase complex
    b. 13α-demethylase complex
    c. NADPH reductase
    d. Lanosterolase
A

a. 14α-demethylase complex

39
Q

Which of these motifs is not present in the Lanosterol 14α-demethylase complex?
a. Heme-Binding Motif
b. Oxygen Binding Motif
c. PER
d. EXXR
e. SER

A

e. SER

40
Q

What class of protein is Lamin β Receptor?
a. Dehydrogenase
b. Lyase
c. Reductase
d. Isomerase

A

c. Reductase

41
Q

What Co-Factor does Lamin β Receptor require?
a. NADPH
b. NADP +
c. ATP
d. ADP

A

a. NADPH

42
Q

How do we know that Lamin β Receptor catalyzes an unfavorable reaction?
a. Loss of conjugation results in the product having a higher ground state energy than the
substrate
b. The oxidation of NADPH releases a large amount of energy
c. Neither A nor B
d. Both A and B

A

d. Both A and B

43
Q

What Isomerase is used to catalyze the reaction of Zymosterol to Dehydrolathosterol?
A. Glucose isomerase
B. Transferase
C. Emopamil-Binding Protein
D. Ligase

A

C. Emopamil-Binding Protein

44
Q

What Cofactor is required in the isomerization reaction of Zymosterol to
Dehydrolathosterol?
A. Mg 2+
B. Cu+
C. ADP
D. No Cofactor is required

A

D. No Cofactor is required

45
Q

How many Transmembrane helices make up the active site of Emopamil Binding
Proteins?
A. 3
B. 5
C. 7
D. 4

A

B. 5

46
Q

What is the specific name of the second reaction for the first step?
a. Acid - Base Reaction
b. Claisen Condensation Reaction
c. Nucleophilic Acyl Substitution
d. Condensation Reaction

A

b. Claisen Condensation Reaction

47
Q

What kind of enzyme class in step ones reaction?
a. Transferase
b. Isomerase
c. Ligase
d. Hydrolase

A

a. Transferase

48
Q

What way is the reaction favored for step one? Why?
a. Unfavorable; ΔG°’ = +26.1
b. Favorable; ΔG°’ = -26.1
c. Favorable; ΔG°’ = -16.4
d. Unfavorable; ΔG°’ = +16.4

A

a. Unfavorable; ΔG°’ = +26.1

49
Q

What is the rate limiting step in the synthesis of cholesterol?
a. Step 3: 3-hydroxy-3-methylglutaryl-CoA to Mevalonic Acid
b. Step 4: Mevalonic Acid to Mevalonate-5-phosphate
c. Step 11: Squalene to 2,3 oxidosqualene
d. Step 12: 2,3 oxidosqualene to lanosterol

A

a. Step 3: 3-hydroxy-3-methylglutaryl-CoA to Mevalonic Acid

50
Q

What cofactor is required for the conversion of 3-hydroxy-3-methylglutaryl-CoA to Mevalonic
Acid?
a. Adenosine Triphosphate (ATP)
b. Thiamine pyrophosphate (TPP)
c. Nicotinamide Adenine Dinucleotide Phosphate (NADPH)
d. Tetrahydrofolate

A

c. Nicotinamide Adenine Dinucleotide Phosphate (NADPH)

51
Q

What happens in the general mechanism of the conversion of 3-hydroxy-3-methylglutaryl-CoA
to Mevalonic Acid?
a. A phosphorylation
b. Two successive hydride transfers
c. An isomerization
d. An acyl substitution

A

b. Two successive hydride transfers

52
Q

What is the cofactor in step 4 of the reaction pathway of Mevalonate to Mevalonate-5-phosphate?
a. Zn 2+
b. Acetyl-CoA
c. Mg 2+
d. Cl-

A

c. Mg 2+

53
Q

What kind of inhibition is Mevalonate Kinase subject to?
a. Competitive
b. Non-Competitive
c. Un-Competitive
d. All of the above
e. None of the above

A

a. Competitive

54
Q

In Reaction Step 4 (Mevalonate-> Mevalonate-5-phosphate), from what part of mevalonate did
the basic amino acid Asp204 remove a proton to create a nucleophile?
. 3’-OH
b. 1’-OH
c. 1’-Carbonyl
d. 5’-OH

A

d. 5’-OH

55
Q

What is the name of the enzyme that catalyzes reaction number 5?
a. Mevalonate kinase
b. Thiolase
c. Phosphomevalonate kinase
d. HMG-CoA reductase

A

c. Phosphomevalonate kinase

56
Q

What kind of reaction is Step 5 (mevalonate-5-phostphate → mevalonate-5pyrophostphate)?
i. Phosphorylation
ii. oxidation reduction
iii. decarboxylation
iv. ATP hydrolysis
a. i,ii,iii
b. iv,ii
c. ii,iii
d. i,iv

A

d. i,iv

57
Q

Is the reaction of step 5 in cholesterol synthesis favorable or unfavorable?
a. Favorable
b. Unfavorable
c. Reaction doesn’t occur
d. Unable to determine

A

a. Favorable

58
Q

What is FPP composed of?
a. GPP & IPP
b. IPP & IPP
c. FPP & GPP
d. FPS & IPP

A

a. GPP & IPP

59
Q

What is FPP’s class type?
a. Monoterpene
b. Limonene
c. Sesquiterpene
d. Diterpene

A

c. Sesquiterpene

60
Q

What are Bisphosphonates?
a. A group of drugs that are used to slow bone loss
b. A group of drugs that are used to increase bone loss
c. A group of drugs that causes temporary paralysis
d. A group of drugs that are used to slow metabolism

A

a. A group of drugs that are used to slow bone loss

61
Q

What class of enzyme is squalene synthase?
a. Hydrolase
b. Isomerase
c. Ligase
d. Lyase

A

c. Ligase

62
Q

How many molecules of farnesyl pyrophosphate are required to create squalene?
a. 2
b. 3
c. 8
d. 1

A

a. 2

63
Q

The head-to-head reductive dimerization of FPP to form squalene is favorable because of
a. The oxidation of NADPH
b. The reduction of NADPH
c. The oxidation of magnesium
d. The reduction of magnesium

A

b. The reduction of NADPH

64
Q

In the enzyme Squalene Monooxygenase (Step 11: squalene  2,3-oxidosqualene) what are the
3 domains within the catalytic domain?
a. FAD-binding domain, Substrate/inhibitor binding domain, C-terminal domain
b. S-domain, L-domain, N-domain
c. Monomer A, Monomer B, Monomer C
d. Catalytic domain, NADPH-binding domain, C-domain

A

a. FAD-binding domain, Substrate/inhibitor binding domain, C-terminal domain

65
Q

In Step 11 (squalene  2,3-oxidosqualene), the enzyme Squalene Monooxygenase utilizes
multiple cofactors/coenzymes. Choose the cofactors/coenzymes involved that are paired with
the correct functions.
a. NADPH; reductant
b. O2; oxidant
c. FAD; stabilization of catalytic residues
d. All of the above
e. a and b only

A

d. All of the above

66
Q

Which of the following class of enzymes does squalene monooxygenase fall under? Be as
specific as possible. (Hint: remember that squalene monooxygenase catalyzes the reaction of
squalene to 2,3-oxidosqualene. It requires NADPH and Oxygen to create an epoxide rather than
a hydroxyl group).
a. Oxidoreductase (Class 1)
b. Epoxidase (Class E)
c. Hydroxylase (Class 3)
d. Lyase (Class 4)
e. Ligase (Class 6)

A

b. Epoxidase (Class E)