Page 134 - Medicinal Chemistry Self Assessment

Section 3 General Self Assessment Answers

2.7 Drug Metabolism

2.7

Drug Metabolism
1. Heroin is a synthetic derivative of the naturally occurring opioid analgesic morphine. Given its illicit
nature, heroin is not subject to Food and Drug Administration (FDA) regulation; therefore, the actual
1. Heroin is a synthetic derivative of the naturally occurring opioid analgesic morphine. Given its illicit
composition of a given heroin batch varies significantly. The three molecules drawn below represent the
three major components found within a batch of heroin. The users’ intense rush has been attributed to
morphine. Which phase I transformation is responsible for the conversion of heroin to morphine?
the conversion of heroin into morphine. Which phase I transformation is responsible for the conversion of
heroin to morphine?

Heroin Morphine

2. Estradiol, the estrogen component of many oral contraceptives, undergoes a phase II conjugation then
Answer
Heroin is the diacetyl ester of morphine. Two successive phase I ester hydrolysis reactions are responsible
reabsorbed (at least in part). Consider the structure of estradiol drawn below and do the following:
for the conversion of heroin to morphine.
a. Modify the structure drawn below to show the product of a sulfate conjugation (phase II

transformation).
2. Estradiol, the estrogen component of many oral contraceptives, undergoes a phase II conjugation reaction
to produce a metabolite that is eliminated via a fecal route (at least in part). The conjugated hormone
b. Which enzyme is required to make this sulfate conjugate?
undergoes a process called enterohepatic recycling. In this process the sulfate conjugate is cleaved by gut
Answer: Sulfotransferase (SULT)
bacteria to regenerate the active drug, which is then reabsorbed (at least in part). Consider the structure
of estradiol drawn below and do the following:
c. Which deconjugating enzyme catalyzes removal of the sulfate group thus allowing for
a. Modify the structure drawn below to show the product of a sulfate conjugation (phase II
enterohepatic recycling?
transformation).
b. Which enzyme is required to make this sulfate conjugate?
Answer: Sulfatase
Answer
Sulfotransferase (SULT)

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