Deck 11: The Cytochromes P450 and Nitric Oxide Synthases

Question 1

In what organ does the hydroxylation at the 1 position of 25-hydroxy vitamin D3 occur, forming the active form of the vitamin?

A) Adrenals
B) Intestines
C) Kidney
D) Liver
E) Skin

Answer 1

Kidney

Question 2

How is the action of NO terminated?

A) Diffusion away from site of action
B) Enzymatic degradation
C) Interaction with its target molecule
D) Metabolism of NO
E) Reuptake into cells

Answer 2

Interaction with its target molecule

Question 3

The iron in cytochrome P450 can form six coordinate-covalent bonds. Four are with nitrogen on the pyrrole rings and one is the oxygen-binding site. To what is the other bond targeted?

A) Aspartate
B) Cysteine
C) Histidine
D) Lysine
E) Serine

Answer 3

Cysteine

Question 4

All of the following statements are correct EXCEPT which one?

A) Cytochrome P450, a heme protein, reacts directly with oxygen.
B) One would expect cytochrome P450 to be inhibited by carbon monoxide.
C) NADPH, flavoprotein and an iron-sulfur protein react in sequence to reduce cytochrome P450 in some steroidogenic organs.
D) Using the heavy isotope of oxygen 18O2 it can be shown that cytochrome P450 catalyzes a reaction in which both atoms of oxygen are found in a typical product designated ROH.
E) Cytochrome P450 is located in the endoplasmic reticulum in liver, and both the endoplasmic reticulum and mitochondria in steroidogenic tissue (such as the adrenal).

Question 5

From what electron donor may the second electron that enters the microsomal cytochrome P450 cycle come?

A) An iron-sulfur protein
B) Cytochrome b5
C) Cytochrome b5 reductase
D) Cytochrome c
E) NADH

Question 6

Why does a polymorphism in CYP2D6 decrease the efficacy of codeine?

A) Alters the number of AhR
B) Decreases uptake of codeine by the brain
C) Increases excretion of codeine
D) Increases Phase II metabolism
E) Slows formation of morphine

Question 7

The absorption maximum at 450 nm of cytochrome P450 requires that the iron be in the Fe++ state and bound to a specific molecule. What is this molecule?

A) CO
B) CO2
C) H2O
D) NADPH E . O2

Question 8

Has the LEAST involvement in the oxidative burst:

A) Glucose-6-phosphate dehydrogenase
B) Glutathione peroxidase
C) Myeloperoxidase
D) NADPH oxidase
E) Superoxide dismutase

Question 9

NADPH is a two electron donor. Heme can only accept one electron. How is this accommodated in the microsomal electron transport chain?

A) NADPH binds heme, leaves, and rebinds heme
B) NADPH donates on electron to an iron-sulfur protein
C) NADPH gives electrons to a flavoprotein with two flavin groups
D) NADPH gives electrons to two flavoproteins with one flavin group each
E) NADPH transfers only one electron

Question 10

Which of the following conversions involves a cytochrome P450-catalyzed reaction?

A) cholesterol to estradiol
B) glucose to glycogen
C) glucose 6-phosphate to ribose 5-phosphate
D) pyruvate to acetyl-CoA
E) propionyl-CoA to succinate

Question 11

What is the most common enzyme deficiency in adrenal hyperplasia?

A) CYP11A1 (scc)
B) CYP21A2
C) CYP24A1
D) CYP3A4
E) CYP7A1

Question 12

Nitric oxide is produced in cells from which of the following amino acids?

A) arginine
B) histidine
C) lysine
D) glutamine
E) asparagines

Question 13

One substrate for the constitutive endothelial isoform of nitric oxide synthase (eNOS) is

A) acetylcholine.
B) 3',5'-adenosine monophosphate.
C) arginine.
D) citrulline.
E) sildenafil (Viagra).

Question 14

Why did administration of erythromycin make the use of Seldane in a patient contraindicated?

A) Erythromycin accelerates excretion of Seldane
B) Erythromycin binds to a product of Seldane metabolism
C) Erythromycin caused Phase II metabolism of Seldane
D) Erythromycin induces metabolism of Seldane
E) Erythromycin inhibits metabolism of Seldane

Question 15

Nitric oxide synthases have two domains. What bridges the domains to allow electron transfer between them?

A) Adrenodoxin
B) Calmodulin
C) Cytochrome b5
D) Flavin
E) Heme

Question 16

What is the general characteristic of substrates for cytochrome P450?

A) Aromatic
B) Basic
C) Charged
D) Hydrophilic
E) Lipophilic

Question 17

The protein cytochrome P450 found in liver microsomes

A) is reduced by NADPH directly without a reductase enzyme.
B) binds hydroxylatable substrates and oxygen.
C) requires catalytic amounts of a non-heme iron protein called ferritin.
D) converts lipophilic compounds into conjugates with sulfate or glucuronic acid.
E) All of the above.

Question 18

What is the prosthetic group of cytochrome P450?

A) Flavin
B) Heme
C) Iron-sulfur
D) Pyridine nucleotide
E) Thiamine

Question 19

All of the following statements regarding the cytochrome P450-dependent hydroxylation of drugs are true EXCEPT which one?

A) The hydroxylation of drugs requires NADPH.
B) The oxygen atom incorporated into the drug molecule is derived from molecular oxygen.
C) The hydroxylation of drugs is associated with the utilization of protons.
D) The oxygen atom incorporated into the drug molecule is derived from water.
E) The hydroxylation of drugs is associated with the formation of water.

Question 20

The conversion of toxic organic peroxides to alcohols in the liver requires an enzyme which utilizes reduced glutathione and contains in its active site:

A) Cobalt
B) Copper
C) Selenium
D) Iron
E) Tetrahydrofolate

Question 21

What is the mechanism of induction by substrates of cytochrome P450?

A) G-protein interaction
B) Intracellular receptor binding
C) Membrane-bound receptor binding
D) Phospholipase C
E) Ras (insulin-like) cascade

Question 22

Which class of hormones are synthesized by a series of cytochrome P450s?

A) Amino acid derivatives
B) Cytokines
C) Peptides
D) Steroid
E) Thyroid

Question 23

Why might inhibition of CYP19A1 be therapeutic for breast tumors?

A) Increase in testosterone synthesis
B) Inhibition of estrogen metabolism
C) Inhibition of synthesis of estrogens
D) Production of estrogen antagonists
E) Reduction of binding to p53

Question 24

Which has the most negative potential?

A) FAD
B) FMN
C) NADPH
D) cytochrome P450 heme
E) cytochrome P450 heme plus substrate

Question 25

The biotransformation reactions of detoxication occur primarily in

A) liver.
B) kidney.
C) muscle.
D) brain.
E) uterus.

Question 26

Approximately how many genes are there for different isoforms of cytochrome P450 are there in humans?

A) 10
B) 20
C) 30
D) 40
E) 60

Question 27

The functional metabolite of nitroglycerin is:

A) Nitrous oxide
B) Nitrate
C) Nitrite
D) Nitrogen peroxide
E) Nitric oxide

Question 28

How much more steroid hormone does fetal adrenal cortex make than adult adrenal cortex?

A) 10 times
B) 100 times
C) 1000 times
D) The same
E) Twice

Question 29

All of the following statements about the mixed function oxidase systems are correct EXCEPT which one?

A) Many times a hydroxylation reaction is involved.
B) It is often considered a detoxification reaction in the liver.
C) It can involve an O-dealkylation of N-dealkylation of substrate.
D) It may result either in inactivation of drugs or formation of a more active compound.
E) Its activity does not vary upon administration of a variety of drugs or other foreign compounds.

Question 30

Which of the following enzymes is important in protecting the cell from the potential toxicity of superoxide anion and its derivatives?

A) superoxide dismutase
B) cytochrome oxidase
C) succinate dehydrogenase
D) FoF1_ATPase

Question 31

How many bimolecular oxygen molecules are used by CYP11A1 (side-chain cleavage enzyme)?

A) 1
B) 2
C) 3
D) 4
E) 5

Question 32

Where are liver cytochrome P450 enzymes located?

A) Cytosol
B) Deeply embedded in the ER
C) Lumen of the ER
D) Plasma membrane
E) Surface of the ER

Question 33

What is the major role of NOSII?

A) Cytotoxicity in the immune response
B) Dilation of blood vessels in the periphery
C) Perception of pain
D) Potentiation of learning and memory
E) Relaxation of skeletal muscle

Question 34

The toxic form of benzoapyrene binds covalently to DNA. What mechanism does benzoapyrene use to potentiate its toxicity?

A) It binds covalently to cytochrome P450
B) It increases the amount of AhR
C) It induces cytochrome P450 and its own metabolism
D) It inhibits glucuronidation
E) It inhibits its own further metabolism

Question 35

In the relaxation of arterial smooth muscle, nitric oxide (NO)

A) antagonizes a bradykinin receptor.
B) inhibits a phosphodiesterase.
C) opens a K+ channel.
D) stimulates a guanylyl cyclase.
E) triggers a release of lumen Ca2+

Question 36

The liver microsomal monooxygenase system containing cytochrome P450 can modify drugs by

A) formation of a sulfate group.
B) addition of an acyl residue.
C) formation of an hydroxyl group.
D) addition of a glucuronic acid residue.
E) formation of a disulfide bond.

Question 37

What is the ratio of cytochrome P450 to cytochrome P450 reductase in the microsomal electron transport chain?

A) 1:1
B) 20:1
C) 100:1
D) 1:20
E) 1:100

Question 38

NADPH-cytochrome P450 reductase is found principally in the

A) plasma membrane.
B) nuclear envelope.
C) cytoplasm.
D) endoplasmic reticulum.
E) lysosomes.

Question 39

What is the major mechanism of action of NO?

A) ATP to cAMP
B) Binding to intracellular receptors
C) GTP to cGMP
D) Phosphoinositol phosphate to DAG
E) Ras cascade

Question 40

Cytochrome P450 cannot or does not:

A) Cause carcinogen activation
B) Detoxify some toxins
C) Facilitate excretion
D) Be induced
E) Make xenobiotics more lipid soluble

Question 41

A complex that uses oxygen as a substrate is:

A) NADH-Q reductase
B) Pyruvate dehydrogenase
C) Cytochrome P450
D) Cytochrome reductase

Question 42

Drug-metabolizing enzymes occur predominately in which subcellular fraction?

A) Plasma membrane
B) Nucleus
C) Mitochondria
D) Endoplasmic reticulum
E) Lysosomes

Question 43

Other than liver, in which organ is CYP3A4 most abundant?

A) Adrenals
B) Intestine
C) Kidney
D) Lungs
E) Skin

Question 44

The biotransformation reactions of detoxication occur primarily in

A) liver.
B) kidney.
C) muscle.
D) brain.
E) uterus.

Question 45

What is kind of enzyme is a monooxygenase?

A) One that catalyzes formation of an epoxide
B) One that incorporates O2 into a substrate
C) One that inserts one atom of oxygen into a substrate
D) One that produces superoxide
E) One that removes hydrogens from a substrate

Question 46

What source donates electrons directly to adrenodoxin in the mitochondrial cytochrome P450 reaction?

A) FAD
B) FeS
C) FMN
D) Heme
E) Pyridine nucleotide

Question 47

The functional metabolite of nitroglycerin is:

A) Nitrous oxide
B) Nitrate
C) Nitrite
D) Nitrogen peroxide
E) Nitric oxide

Question 48

What is the substrate for the formation of NO?

A) Arginine
B) Asparagine
C) Creatine
D) Glutamine
E) Lysine

Question 49

Oxidation of which of the following molecules in vascular endothelial cells produces the nitric oxide that is transported by hemoglobin?

A) 3',5'_AMP (cyclic_AMP)
B) acetylcholine
C) arginine
D) heme
E) urea

Question 50

Approximately what percentage of therapeutic drugs are metabolized by CYP3A4?

A) 1
B) 5
C) 20
D) 50
E) 100

Question 51

In the cytochrome P450 cycle, what binds first?

A) An electron on oxygen
B) An electron on the iron atom
C) Oxygen
D) Substrate
E) Water