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Welcome everyone
to Chapter 11 of
this short talk series on
nuclear receptors a
therapeutic targets.
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Chapter 11 and the subsequent
chapter will deal with
the peroxisome
proliferator-activated receptors,
abbreviated typically as PPAR.
The PPARs represent
the NR1C family
of nuclear receptors,
and there are three
PPAR subtypes.
Alpha, Gamma, and
the third subtype
is referred to as
either Beta or Delta.
PPAR Delta is more common,
and I will stick to that here.
In this chapter, we will mainly
deal with PPAR Alpha and Delta,
and PPAR Gamma, then is the
main topic of Chapter 12.
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The PPARs bind various types
of lipids and fatty acids.
It's hard to speak of
one endogenous ligand.
Several unsaturated
fatty acids bind
PPARs in the low
micromolar range,
and eicosanoids and oxidized
polyunsaturated fatty acids
also act as PPAR ligands.
Additionally, the thyroid
hormone metabolite tetrac and
oxidized vitamin E metabolites
have been identified
as PPAR modulate.
Agonist binding
to PPAR typically
involves interaction
with a series of polar
and charged a minor acid
side chains in or in
close proximity
to the activation
function two located
in helix 12.
This is shown here on the left
as example for PPAR Gamma.
These side chains and
bound water molecules,
together with a typically
acidic group in the ligand,
form a hydrogen bond
network that stabilizes
helix 12 in its active
conformation and position,
then leading to PPAR activation.
