Study Set Content:
METHYLATION cofactor
S-adenosyl methionine (SAME)
addition of gluta
molecule, which is a tripeptide producing molecule of
glycine, cysteine and glutamic acid to an electrophilic
substrate
GLUTATHIONE CONJUGATION
GLUTATHIONE CONJUGATION
Electrophilic centre, alkyl halides, epoxides
responsible for the
reaction of glutathione with electrophiles,
(halides and epoxides)
Glutathione-S-transferase-
adding of n-acetyl group to primary
amines.
ACETYLATION
ACETYLATION
Primary aromatic amines, sulfonamides
o N-acetyltransferase
are relatively faster than P450-catalyzed
reactions, thus effectively accelerating drug biotransformation.
PHASE II REACTIONS
Drug conjugations were once believed to represent
terminal inactivation events and as such have been viewed
as(blank) reactions.
“true detoxification”
Certain conjugation reactions:
of nonsteroidal anti-
inflammatory drugs
acyl glucuronidation
of N -hydroxyacetylaminofluorene
O-sulfation
may lead to the
formation of reactive species responsible for the
toxicity of the drug
N –acetylation of isoniazid
also known to activate the orally active prodrug minoxidil
into a very efficacious vasodilator, and morphine-6-glucuronide is
more potent than morphine itself.
Sulfation
Phase I reactions
Hydrolysis
Reduction
Oxidation
What are the 2 general sets of modification that occur in
biotransformation?
A. Phase I Reactions
B. Phase II Reactions
What happens in phase I?
Lipophilic molecules are converted into more
polar molecules, through
Introduction or
unmasking of polar functional group.
What type of reactions occur in Phase I?
Oxidation, Reduction, and Hydrolysis
What happens in Phase I? Formation of a (blank) between
functional groups on the parent drug and
another substrate
covalent linkages
What substrates are added in Phase II conjugation
reactions?
Glucuronate, Acetic acid, Glutathione, Sulfate
In what organ do Phase I and Phase II occur?
liver
Where do these reactions occur on a cellular level
Phase I-
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