Biliverdin reductase turns
out to be one of the most
diverse and amazing proteins
in the entire body.
The number of things that it's
involved in is astonishing.
Biliverdin reductase doesn't
just catalyze the reaction
that I've shown you to convert
biliverdin into bilirubin.
But it also is a
Meaning, it is able to add phosphates
onto all three of those amino acids.
And we've seen that kinases like this are
very important in the signaling process.
So not only as biliverdin.
Reductase is important in the
metabolism of bilirubin,
but it's also potentially important
as a signaling component.
In addition to that, biliverdin
reductase affects insulin signaling.
Insulin signaling we have seen
as important for managing
the concentration of glucose
in the bloodstream.
Biliverdin reductase, in addition, may block
the movement of glucose into the cell.
This was something insulin is trying
to stimulate in the first place.
Biliverdin reductase may play a role,
therefore, in insulin resistance.
Insulin resistance happens when cells no
longer are able to respond to insulin,
and as a consequence,
don’t take up glucose.
So this could be a very important
player in that process.
Biliverdin has a
leucine zipper domain.
Now you remember from other
talks in this series
that leucine zippers are very important
both for protein, protein interactions
and also for protein DNA interactions
as occurs with transcription factors.
Biliverdin reductase therefore
may act as a transcription factor.
And finally, biliverdin reductase may
control cyclic AMP-related genes
as it's seen in signaling pathways
such as the beta adrenergic receptor.
This, as I said, is one of the most
interesting proteins that's found in cells.
Now the biochemistry of bilirubin is
important consideration for other
things besides the reactive oxygen
species that I've described.
Bilirubin is not very soluble in the
aqueous environment of our cells.
So the reaction that I'm showing
next here is to facilitate the
solubility of bilirubin or a
bilirubin component in water.
This involves the addition
of glucuronic acid
as you can see on the
screen to bilirubin.
Glucuronic acid is a very water soluble
molecule so it's attachment to bilirubin
to make bilirubin diglucuronide facilitates
bilirubins dissolving in water.
This reaction is called a conjugation
and the conjugation of the
bilirubin with the diglucuronide
enables bilirubin now to be dissolved.
We see in the process that two
waters are split out to make that.
And the product, as I said,
diglucuronide is water soluble.
You can see the reaction, the starting
material shown in the green square on the left
that becomes the green circled portion or
the green outlined portion on the right.
Using this, you can clearly see the addition
of where the glucuronic acids occurs.
The endo reaction
that's happening here,
the precursor is known
as UDP-glucuronic acid.
UDP is simply a carrier.
It is an activated intermediate
that facilitates the donation
of the glucuronic acid to the
bilirubin as we see here.
The products or the reaction
of course being two
UDP molecules shown
in the lower right.
The reaction here is catalyzed by
the enzyme glucuronyltransferase.
Now as I said before, this conjugation
creates a soluble form of bilirubin.
We call that conjugated form
because it's conjugated
to glucuronic acid and
it dissolves in water.
This allows bilirubin
to be easily eliminated
through the bile and the
feces or via the urine.
Bile of course is an
The insoluble form of bilirubin
is called the unconjugated
form because it has no
glucuronic acid attach to it.
It's the glucuronic acid that's
making bilirubin becomes soluble.
This form of bilirubin can circulate
in the bloodstream fairly readily
attached to or bound to the
protein known as albumin.
Now one of the problems that
happens with this system
is that bilirubin in this way
is not filtered by the kidneys.
It doesn’t get eliminated
and can ultimately result
in the formation of the
disease known as jaundice.