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0:00
Welcome. My name is
Abby Collier and this
lecture is about
UDP glucuronosyltransferases
and they are
an enzyme set that I
will be referring to
as UGTs throughout the talk.
0:14
The learning objectives
for this lecture
are to understand the
role of glucuronidation
which is the reaction
performed by
the UGTs in the metabolism
of endogenous compounds
in the body as well as
antibiotics which are compounds
from outside of the human body.
We want you to learn about
the co-substrates of
UGTs and their reactions
and where they
take place in the cell
and in the human body and
understand the complexity
of the UGT enzyme family.
This includes learning
probe substrates as well as
bilirubin metabolism in
the human body so that you
understand genetic diseases
and syndromes associated
with these enzymes and
their roles in adverse
drug reactions.
0:57
This picture shows the
phases of what we call
xenobiotic metabolism
and an example
is using the drug phenytoin.
From the top of the slide
you can see phenytoin undergoing
a Phase I metabolism
reaction which is
primarily reduction and
oxidation and then from
the metabolite
4-hydroxphenytoin through
a Phase II metabolism reaction
performed by the UGTs
to a glucurinide.
On the right hand
side in orange,
you can see how
phenytoin goes from
a very lipophilic drug to
a slightly water
soluble metabolite to
a highly water soluble
metabolite through
Phase II and this
enables excretion.
1:39
The Phase II biotransformation
enzymes also called
conjugating enzymes
are transferases
that primarily detoxify
the human body.
They are also found in other
animals insects and plants.
The reaction products
performed with
conjugation are far more soluble
and are usually
excreted by kidneys in
the urine or sometimes
in the bile.
These Phase II enzymes are what
we call bi-substrate enzymes.
They work on the
molecule of interest.
But they also use a
secondary molecule
to transfer motese from.
The enzyme reaction is to
transfer a component of the
co-substrate or all of it to
the substrate and
second from the bottom,
you'll see an example
of phenyl plus UDPGA,
which is the co factor
or the bi-substrate for
the UGT enzyme becoming
phenyl glucurinide plus UDP.
Although many phase
two enzymes work
on metabolites as shown
in the previous slide,
they can also work directly
on the drug chemical or
compound of interest.
