0:00
Hello. I'm Ann Daly.
For the next 40 minutes or so,
I'm going to talk to you
about phase II metabolism.
0:10
In this talk, I will
start by considering
general aspects of each
phase II reaction,
including issues such as
the biochemical properties
of each enzyme and some
typical drug substrates.
I will then go on to consider
pharmacogenetic aspects of
selected phase II reactions.
Those that are most
important in my view.
Phase II metabolism involves
the conjugation of drugs
0:37
and other related
compounds with groups
such as glucuronic
acid and sulfate.
This usually makes
these compounds
more soluble and
easy to excrete.
Many compounds undergo phase I
metabolism prior to phase II,
but this is not always the case.
Phase II metabolism is
usually detoxicating,
but there are some
exceptions to this.
1:08
This slide summarises the
main conjugation reactions
involved in human drug and
xenobiotic metabolism.
Some endogenous compounds are
also metabolised by
these reactions.
Conjugation with glucuronic
acid is carried out by
the UDP-glucuronosyltransferases
and can occur
at hydroxyl, carboxyl, amino
and sulfhydryl groups.
Sulfate conjugation or
sulfation is carried out by
sulfotransferases and occurs
at amino and hydroxyl groups.
Methyl group conjugation
occurs at hydroxyl,
amino and sulfhydryl groups
and is performed by
methyltransferases.
Acetyltransferases conjugate amino and
hydroxyl groups with acetyl groups.
Amino acid conjugation
involves more than one enzyme
and results in the conjugation
of carboxyl groups
with amino acids
such as glycine.
Finally, glutathione
S-transferases conjugate
electrophilic compounds
containing groups such as
epoxide and organic
halides with glutathione.
