0:00
Hello.
I'm Ann Daly.
And in the next 50
minutes or so I'm going
to introduce you to the CYP2
cytochrome P450 family and its role
in drug metabolism.
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In terms of number of
members, CYP2 is the largest
human cytochrome P450
family, with about 30%
of all human isoforms found here.
There are over 20 different
subfamilies in CYP2.
But I'm going to concentrate
on the main subfamilies that
contribute to drug metabolism here.
As shown, there are five of
these subfamilies, CYP2A,
CYP2B, CYP2C, CYP2D, and CYP2E.
Each of these contain
between one and three
drug metabolizing isoforms.
Other important CYP2 subfamilies
include CYP2S and CYP2J.
But I'm not going to consider
these further as they mainly
metabolize endogenous
compounds rather
than drugs and other xenobiologics.
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The genes that encode
members of the CYP2 family
are all made up of nine exons,
with each of these exons coding
for part of the mature enzyme.
Each isoform is the product
of an entirely separate gene.
But all the genes show
a lot of homology.
The homology between
different subfamilies,
such as CYP2A and CYP2B, is between
40% and 55% at the protein level.
But two isoforms
from the same family
show homology of more
than 55% at protein level.
Different subfamilies are all
derived from a common ancestor
but in the course of evolution
have generally migrated
to different chromosomal locations.
If we concentrate on the drug
metabolizing subfamilies,
CYP2A and CYP2B are found close
to each other on chromosome 19.
CYP2C and CYP2E are both
found on chromosome 10
but at different locations.
And CYP2D is found on chromosome 22.
Where there is more than one
isoform in the same subfamily,
these genes will be side by
side on the same chromosome.
