Which of the following statements is FALSE regarding the binding of estradiol to the estrogen receptor?
The alcohol and phenol groups of estradiol are important hydrogen bonding groups when estradiol binds to the binding site.
The aromatic ring is not important in the binding process.
The hydrophobic skeleton of the molecule forms hydrophobic and van der Waals interactions with the binding site.
The binding site into which estradiol fits is spacious except for the region accepting the aromatic ring.
Which of the following statements is not true regarding the actions of the estrogen receptor?
Binding of estradiol causes dimerization of the receptor.
Binding of estradiol causes a conformational change in the receptor.
A helical section of the receptor protein shifts position to seal estradiol into the binding site and reveals a hydrophobic region called the deactivating function region.
A coactivator protein binds to complete a nuclear translation factor.
In the absence of hormone, estrogen receptor is not bound to DNA but to Hsp90. Estrogen binding displaces the receptor from Hsp90 and allows the formation of receptor dimers, which bind DNA and stimulates gene transcriptions.
Which of the following statements is the closest description of Phase I metabolism?
Reactions which add a polar molecule to a functional group already present on a drug or one of its metabolites.
Reactions which as a polar functional group to a drug.
Which of the following statements is the closest description of Phase II metabolism?
Which of the following enzymes is not involved in catalyzing a Phase I metabolic reaction?
Flavin-containing monooxygenase
Monoamine oxidases
Glucuronltransferase
Esterases
Where in the cell is cytochrome P450 located?
Mitochondrial inner membrane
Cytosol
Mitochondrial matrix
Endoplastmic reticulum
All of the following are detoxifying agents, except:
Glycine
Glutathione
Glucuronic acid
Glycogen
All of the following are true for cytochrome P450, except:
Is also called mixed function oxidase
Uses NADPH
Associated with smooth endoplasmic reticulum
Is an allosteric enzyme
All of the following compounds are detoxified by sulfation, except:
Indole
Phenol
Cresol
Benzoic acid
All of the following are correct about a molecule designated as a cytochrome P450 except:
It contains a heme as a prosthetic group
It catalyzes the hydroxylation of a hydrophobic substrate
It may accept electrons from NADPH
It undergoes a change in the heme iron upon binding a substrate
It comes from the same gene family as all other cytochrome P450
Flavoproteins are usually intermediates in the transfer of electrons from NADPH to cyt P450 because:
NADPH cannot enter the membrane.
Flavoproteins an accept two electrons from NADPH and donate them one at a time to cytP450.
They have a more negative reduction potential than NADPH so accept electrons more readily.
As proteins, they can bind to cyt P450 while the nonproteins NADPH cannot.
They contain iron-sulfur centers.
Benzo[a]pyrene, a xenobiotic produced by combustion of a variety of substances:
Induces the synthesis of cytochrome P450.
Undergoes epoxidation by a cytochrome P450.
Is converted to a potent carcinogen in animals by cytochrome P450.
Would be rendered more water-soluble after the action of cytochrome P450.
All of the above
Which medication(s) should not be co-administered with grapefruit juice?
Immune suppressant agent (cyclosporine A)
Warfarin (anticoagulant)
Statin (lovastatin)
Calcium channel blocker (felodipine)
An adult patient has been taking a drug (Drug A) that is highly metabolized by the cytochrome P450 system. He has been on this medication for 6 months. At this time, he is started on a herbal remedy that is an inducer of cytochrome P450 system. You should monitor this patient for:
Increased therapeutic effects of Drug A
Increased adverse effects of herbal remedy
Decreased therapeutic effects of Drug A
Decreased therapeutic effects of herbal remedy
A 25-year-old male is seen in the hospital Emergency Department. He is disoriendted, but states that he has had nausea, vomiting and abdominal pain since he took “too many pain pills.” Upon examination, his eyes appear yellow. Laboratory tests indicate abnormal liver function (as determined by measurements of serum and bilirubin and liver-associated enzymes in the blood). In addition to gastric lavage, what is the appropriate treatment?
N-acetyl cysteine
Atropine
Vitamin K
Albumin via parenteral administration
Fluphenazine
The enzyme NADPH-adrenodoxin reductase is associated with which of the following systems
Mitochondrial P450
ER cytochrome P450
Neuronal nitric oxide synthase
Acetylcholine esterase
Inducible NOS
Indicate which of the following statements concerning Phase I metabolic drug reactions are correct:
Addition of a glucuronyl group is an example of a Phase I reaction
A major source of Phase I reactions is the cytochrome P450 enzyme system located in the liver smooth endoplasmic reticulum
The products of Phase I reactions are usually more lipid soluble than the parent drug.
Addition of a glucuronyl group is an example of a Phase I reaction AND a major source of Phase I reactions is the cytochrome P450 enzyme system located in the liver smooth endoplasmic reticulum
A major source of Phase I reactions is the cytochrome P450 enzyme system located in the liver smooth endoplasmic reticulum AND the products of Phase I reactions are usually more lipid soluble than the parent drug.
____ is responsible for the metabolism of the largest number of drugs.
CYP2D6
CYP3A4
CYP2E1
CYP1A2
When St. John’s wort and irinotecan are ingested concurrently significant decreases in plasma concentration of irinotecan can occur.
DNA ligase uses the energy of ATP to close nicks in DNA and this involves a mechanism which includes
An AMP in a phospho-ester linkage to the 5’-hydroxyl at one side of the nick
An AMP in a phosphor-anhydride linkage to the 5’-hydroxyl at one side of the nick
An AMP in a phosphor-anhydride linkage to the side-chain of a tyrosine in DNA ligase
An AMP in a phosphor-ester linkage to the 3’-hydroxyl at one side of the nick
A linkage of the side-chain of a tyrosine in DNA ligase to the 5’-phosphate at one side of the nick
Cells normally delay replication until DNA damage and replication errors have been repaired because
DNA polymerase cannot function when the DNA is damaged
Replication of damage or mismatched DNA results in mutations
It is not possible to do repair and replication at the same time
Some repair may require recombination, and that cannot be done during replication
All of the following are correct about a Cytochrome P450 enzyme except:
It may accept electrons from a substance such NADPH
It comes from the same gene family as all other Cytochrome P450
Genetic polymorphism in genes for cytochrome P450:
Could cause an individual to metabolize poorly certain drugs
Could cause an individual to metabolize certain drugs more rapidly than normal
Could cause a specific ethnic group to experience more effects with certain drugs
NADHP-cytochrome P450 reductase:
Uses both FAD and FMN as prosthetic groups
Binds to Cytochrome P450 by strong hydrophobic interactions
Requires an iron-sulfur center for activity
Can use NADH as readily as NADPH
Which of the following treatments would increase the likelihood of toxicity resulting from acetaminophen overdose?
Taking a drug which increases cytochrome P450 activity
Taking an agent which increase glutathione intracellular levels
Taking a compound which increases the fluidity of the plasma membrane
Taking a compound which inhibits inducible NOS (2) activity
Taking a compound that increases renal elimination of sulfate conjugates
How does the mismatch repair system distinguish between the parental (i.e. correct) DNA strand and the newly synthesized strand containing the mismatched base?
Thymine in the parental strand of the helix is methylated at GATC
Thymine in the new strand of the helix is methylated at GATC
Adenine in the parental strand of the helix is methylated at GATC
Adenine in the new strand of the helix is unmethylated at GATC
Genes that are “highly expressed” typically possess __________.
Hypoacetylated histones
Hyperacetylated histones
Methylated cytosines
Hypoacetylated histones AND methylated cytosines
Hyperacetylated histones AND methylated cytosines
Which of the following statements is FALSE?
The steroid-receptor complex interacts with specific regulatory DNA sequences [estrogen response element (ERE)].
The steroid-receptor complex binds to corepressors, thereby initiating transcription of the genes.
The binding of an estradiol to its receptor causes a conformational change in the receptor.
The steroid receptors contain both the ligand-binding and DNA-binding domains.
_____ is a chemical reaction of purine deoxyribonucleosides, deoxyadenosine and deoxyguanosine, in which the B-N-glycosidic bond is hydrolytically cleaved releasing a free base.
Deamination
Depurination
DNA oxidation
Uracil DNA glycosylase
Match the following types of DNA damage to DNA repair system responsible for their repair.
O6-alkylguanine DNA alkyltransferase (AGT)
Mismatch repair (MMR)
Base excision repair (BER)
Nucleotide excision repair (NER)
Photolyase
Which of the following statements are FALSE?
Deamination of 5-methyl cytosine creates a G-T mismatch.
Deamination of cytosine creates a G-U mismatch.
Transcriptionally active regions of DNA have the CpG sequence methylated.
DNA cytosine methylation is associated with gene silencing.
Flavoproteins can accept two electrons from NADPH and donate them one at a time to cytP450.
Which of the following statements regarding NADPH-cytochrome P450 reductase is CORRECT?
Uses both FAD and FMN as prosthetic group.
Binds to cytochrome P450 by strong hydrophobic interaction.
Requires an iron-sulfur center for activity.
Can use NADH as readily as NADPH.
The DNA double helix structure is STABILIZED by all of the following EXCEPT:
Sugar-phosphate backbones
The two glycosidic bonds holding the bases are exactly across the helix
Both internal and external hydrogen bonds
Bases stack together through hydrophobic interactions and van der Waals forces
The enzymatic activity of HIV reverse transcriptase is best described as:
DNA-directed DNA polymerase
RNA-directed DNA polymerase
RNA polymerase
Endonuclease
All are characteristics of RNA-directed DNA polymerase EXCEPT:
Synthesis polynucleotides in the 5’ to 3’ direction
Also called reverse transcriptase
Found in retroviruses
RNAse H activity
All are true
A solution contains DNA polymerase I, Mg2+ salts of dATP, dGTP, dCTP, and dTTP, and an appropriate buffer. Which of the following DNA molecules would serve as a template for DNA synthesis when added to this solution?
A single-stranded closed circle
A single-stranded closed circle base-paired to a shorter linear strand with a 3’-terminal hydroxyl (OH)
A single-stranded closed circle base-paired to a shorter linear strand with a 3’-terminal phosphate
A double-stranded closed circle
The PROOFREADING activity of E. coli DNA polymerases:
Occur after DNA synthesis is complete
Is a function of 5’ 3’ exonuclease activity associated with DNA polymerase itself
Is a function of 3’ 5’ exonuclease activity associated with DNA polymerase itself
Is a function of 3’ 5’ endonuclease activity associated with DNA polymerase itself
An Okazaki fragment is a:
Fragment of DNA resulting from endonuclease action.
Fragment of RNA that is a subunit of the 30S ribosome.
Piece of DNA that is synthesized in the 3’ 5’ direction.
Segment of DNA that is an intermediate in the synthesis of the lagging strand.
The proofreading function of DNA polymerase involves all of the following except:
3’ --> 5’ exonuclease
Base pairing
Detection of mismatched base pairs
Phosphodiester bond hydrolysis
Reversal of the polymerization reaction
Which of the following statements about DNA polymerase reaction is FALSE?
They add deoxyribonucleotide units to a free 3’-hydroxyl (OH) of a primer
All DNA synthesis require a template DNA
The reaction requires nucleoside triphosphate (dATP, dTTP, dCTP, dGTP)
Synthesis polynucleotides in the 3’ to 5’ direction
The enzyme that seals nicks in the dsDNA where a 3’-OH and 5’-phosphate is:
DNA polymerase I
DNA topoisomerase
DNA polymerase III
DNA ligase
Zidovudine (AZT) is a more effective inhibitor of HIV reverse transcriptase than of mammalian cell DNA polymerases because:
AZT crosses the outer mammalian cell membrane more efficiently than it crosses the nuclear membrane.
AZT can be converted to a ribonucleotide triphosphate more efficiently than to a dTTP.
HIV reverse transcriptase can utilize either an RNA or DNA template, whereas mammalian DNA polymerases can on utilize a DNA template.
Mammalian DNA polymerases have a 3’ 5’ exonuclease activity, whereas HIV reverse transcriptase does not.
AZT, the first drug approved use against the human immunodeficiency virus (HIV). Before the drug can inhibit the viral transcriptase, it must be converted to a form of nucleotide by:
HGPRT
Ribonucleotide synthase
Thymidylate synthase
Nucleoside phosphorylase
Thymidine kinase
Acyclovir was one of the first highly selective antiviral agents for Herpes simplex virus. Which of the following statements about acyclovir are TRUE? I. Acyclovir is phosphorylated by virus thymidine kinase to form acyclovir monophosphate II. Acyclovir monophosphate is phosphorylated by cellular kinases to form acyclovir triphosphate III. Acyclovir triphosphate is a competitive inhibitor for DNA polymerase, incorporated into growing polynucleotide chains in the place of guanosine residues
I
II
I, II
II, III
I, II, III
One of the functional differences between DNA polymerases and RNA polymerases is that, unlike DNA polymerases, RNA polymerases
Supply their own template
Do not require a primer
Do not require the DNA to be unwound
Synthesis nuclei acid with the same polarity as the template, rather than anti-parallel
The flow of genetic information in Central Dogma of Biology (included the retroviruses) is as follows:
RNA --> DNA --> proteins
RNA --> DNA --> RNA --> proteins
DNA --> RNA --> proteins
DNA --> RNA --> DNA --> RNA --> proteins
Which of the following statements about Pregnane X receptor (PXR) is FALSE?
It is a member of the orphan nuclear receptor family.
It contains ligand-activated binding domain.
It binds as a heterodimer with the 9-cis retinoic acid receptor (RXR) to xenobiotic response elements.
It is highly expressed in the liver and intestine, the same tissues which CYP3A gene expression is induced.
It is activated by CYP3A inhibitors such as pregnenolone 16a-carbonitrile (PCN)
Prescription drugs (rifampicin, indinavir and paclitaxel) can activate PXR and stimulate CYP3A expression.
The activated nuclear receptor stimulates the expression of target genes by binding to short DNA sequence motifs, termed xenobiotic response elements in the target genes (CYP3A).
If a female patient was already taking an oral contraceptive (i.e., birth control pill), what best describes the advice you would provide to her regarding St. John’s wort?
She should take her St. John’s wort one hour before or two hours after taking her oral contraceptive.
St. John’s wort may increase the metabolism of her oral contraceptive.
St. John’s wort may decrease the metabolism of her oral contraceptive.
Early evidence suggested that there may be an interaction between St. John’s wort and oral contraceptives, but the most recent evidence indicates that this is no longer a concern.
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