0:00
Hello, and
welcome to this presentation
on mammalian flavin-containing
monooxygenases,
which we'll abbreviate as FMOs.
The FMOs represent an
enzyme family that's
an important component of the
body's armamentarium of oxidative
drug metabolizing enzymes.
I am Allen Rettie.
And I will be your guide for this
topic through the next 40 minutes.
0:26
Today's lecture will be divided
into six main sections dealing
with the structure, mechanism,
enzyme multiplicity,
gene regulation, and substrate
specificity of the mammalian FMOs.
We will also devote time to
discussing experimental methods
that permit the differentiation
of FMO catalysis
from that of the cytochrome
P450s, both of which
are present in the microsomal
fraction of the cell.
The presentation will conclude with
suggestions for future research
but begin with some
historical background
and an overview of the enzyme's
general characteristics.
1:06
In the mid-1960s and early
'70s, Dr. Dan Ziegler's group
at the University of Texas at
Austin provided the first evidence
for a second NADPH and oxygen
dependent monooxygenases
system, located in the
endoplasmic reticulum of the cell.
The first such enzyme system was
already known as cytochrome P450,
an enzyme recognized to be
a heme containing protein.
Ziegler's group showed that hog
liver microsome possess tertiary
immune N oxygenase
activity towards substrates
such as N,N dimethylaniline.
The resulting N oxide
metabolite was uncharacteristic
of cytochrome P450, which typically
N, D alkylates tertiary amines.
Subsequent purification
of this new enzyme
revealed that it lacked heme
but contained a flavin cofactor.
Consequently, the enzyme was named
flavin-containing monooxygenases
and assigned a new enzyme
classification number 1, 14, 13, 8.
