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BPS 2110 - Final Exam Questions And 100% Correct Answers
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BPS 2110 - Final Exam Questions And 100% Correct AnswersThe antiviral drug Acyclovir has a strange bioavailability profile resulting in an extremely
low incidence of side effects. Explain in detail how the drug is distributed both in the
body and in virally infected cells. - ANSWER The drug is not phosphorylated by host
kinases. It can freely diffuse in and out of the host cells. Because it is not
phosphorylated, the drug is in the inactive form and cannot interact with polymerases.
Once the drug is phosphorylated by the viral enzyme, host enzymes convert the
mono-phosphate unto a triphosphate. This carries 3 negative charges which inhibits the
triphosphate from escaping the cell. The drug accumulates in cells as the new active
triphosphate can inhibit viral polymerase.
What are the three general types of influenza virus? - ANSWER Type A, Type B, and
Type C.
Which types of influenza virus cause serious disease and which do not? ANSWER Types
A and B cause serious disease, whereas Type C does not.
Why are some forms of the influenza virus more dangerous than others? ANSWER
Because of the high mutation rates that make it very difficult for the immune system to
clear.
Why must a person be vaccinated against influenza yearly? - ANSWER Due to the high
mutation rate, there is a new virus circulating each year.
What does the designation H1N1 denote? - ANSWER The virus is composed of type 1
hemagglutinin and type 1 neuraminidase.
Why do these classify viruses of influenza? It is dependent on the presence of subtypes
of hemagglutinin and neuraminidase on the outside of the virus. These are easily
identified by antibodies, and therefore easily classified.
,What is Hemagglutinin? - ANSWER A viral membrane protein that binds to the sugar
sialic acid. Sialic acid is found on human membrane proteins that the virus uses to gain
entry into the cell.
What is neuraminidase? -ANSWER A viral membrane enzyme that removes sialic acid
from other proteins. Removal of sialic acid from the human proteins on the virus
envelope is necessary to prevent virus particle from sticking to other virus particles.
What is the general strategy that is used to design inhibitors of neuraminidase? -
ANSWER Rational drug design. This would make a drug that resembles the transition
state of the reaction the enzyme catalyzes.
What general type of inhibitor is best used to block enzyme function using rational drug
design? - ANSWER Make a transition state mimic.
What are the advantages of Tamiflu? - ANSWER Decreases the course of illness by 1
day.
What are the disadvantages of Tamiflu? - ANSWER Must be given within the initial
symptom stage of 24 to 48 hr.
-Very expensive
-Supply is limited
-Side effects many
Why Tamiflu is so expensive? - ANSWER Manufacturing is complicated because it
includes hard chemistry and the raw product to be used is of limited material
availability.
Explain how the method of chain termination with electronic chain termination works. -
ANSWER Position a strong electron-withdrawing group proximal to the 3'OH of a
nucleoside. The EWG reduces the nucleophilicity of the OH enough to prevent chain
extension.
,AIDS drugs are ineffective singly but effective in combination. Explain this seeming
paradox. - SOLUTION Given singly, the virus develops resistance to the drug in
remarkably short order due to its high mutation rate. Administration of multiple drugs
makes resistance less likely because the virus would have to evolve too many changes
at once.
What two enzymes of the AIDS virus are used to replicate its genetic information? -
ANSWER -Reverse transcriptase
-RNAse H
What properties of the AIDS virus enzymes contribute to HIV having an exceptionally
high mutation rate? - ANSWER -Reverse transcriptase is a sloppy enzyme making lots of
mistakes.
-RNAse H degrades the viral RNA template as the DNA strand is being synthesized.
Thus, there is no proofreading of this transcription.
What key feature of anti-HIV drug structure has allowed therapies with radically
reduced side effects? - ANSWER Certain pseudoeneatiomer nucleosides are substrates
for host kinases and the resulting nucleotides are substrates for HIV reverse
transcriptase. This leads to chain termination of the viral DNA. Host polymerases will
not accept pseudoenantiomer nucleotides as substrates and so these drugs are
incapable of chain terminating host nucleic acid synthesis.
What is the key structural element that gives rise to this "clean" profile? - ANSWER A
pseudoenantiomer of a natural nucleoside.
What is a pseudoenantiomer? - ANSWER A pseudoenantiomer refers to a stereoisomer
which is not a true enantiomer since it isn't an exact mirror image normally impeded by
steric conformation.
Why does this make 3-TC so selective? - ANSWER The pseudoenantiomer is accepted
by HIV reverse transcriptase and becomes incorporated into viral nucleic acid. The
drug acts like a chain terminator and stops nucleic acid replication. Because it is a
pseudoenantiomer it will not be accepted as a substrate by host polymerases. Because
it does not inhibit any host enzymes or nucleic acid production, it does not produce alot
, of side effects.
What does one mean by the term retrovirus? - ANSWER Virus carries its genetic
information in the form of RNA. The RNA is translated into double stranded DNA inside
the cell.
What is the key enzyme present in the retroviruses that give rise to this behaviour? -
ANSWER Reverse transcriptase.
What general drug strategy has been employed to inhibit this enzyme? - ANSWER
Rational drug design using chain termination and non-natural sugar nucleoside
analogues.
What type of reaction is used in this process to biosynthetically link isoprene units? -
ANSWER An SN2 reaction followed by an E1 reaction.
What percent of the cholesterol in humans is made in the liver? - ANSWER Made in the
liver from saturated and trans fats.
Where in the body is excess cholesterol stored? - ANSWER In the lining of the arterial
walls.
Why is this storage location for cholesterol a problem? - ANSWER As cholesterol gets
deposited there, the artery gets damaged, due to oxidation of the cholesterol into
cholestenone. The artery starts to swell to get rid of the cholestenone and as a result,
the plaques burst. This causes blood clots that block the artery.
What do you call a cholesterol deposit? - ANSWER Plaque
Describe major steps of the development of a cholesterol related obstruction - ANSWER
-Cholesterol in arterial wall.
-Cholesterol is oxidized to cholestenone.
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