Well, the urea cycle is actually
the place where the urea is made
from that previous figure
that I've just showed.
It's therefore important
that we consider the
reactions of the urea cycle
in the slides ahead.
The urea cycle occurs primarily in the
liver and also in the kidney as we saw.
The urea cycle consists of
four different cycle reactions
and one feeder reaction in the
overall process as I will show you.
That involves five different enzymes.
The feeder reaction is shown at the
top, and it involves the incorporation
of one molecule of ammonia
or ammonium, same thing,
and one carbon dioxide.
That creates a molecule that
then feeds into the cycle.
It's necessarily for that reaction to occur
in order for the overall cycle to occur.
So this process I've just described
involves then the incorporation of one
ammonium ion from the feeder reaction
and one amine from
an amino acid.
In this way, both the amines and
the ammonium ions get balanced.
So the output of the cycle is one
molecule of urea per turn of the cycle,
and that means that urea contain
one of its nitrogens from ammonium
and one of its nitrogens from amine.
The net reactions per turn of the cycle
involve the incorporation of two amines,
in this case NH3 coming from ammonium or
NH2 that becomes NH3 coming from an amine.
Carbon dioxide is also needed,
three ATPs and water.
That creates urea, two molecules of
ADP, four phosphates, and an AMP.
Let's consider the reactions
of the urea cycle.
You remember that the very first
reaction is a feeder reaction.
It creates a molecule that then
feeds into the overall cycle.
In that reaction, ammonium ion that's
produced by the catabolic process
of amino acid catabolism is
combined with bicarbonate
to make a molecule of
That's feeder reaction is catalyzed by the
enzyme carbamoyl phosphate synthethase.
In the next reaction, the carbamoyl phosphate
is incorporated into the urea cycle
by combining with the molecule
of ornithine to make citrulline.
That reaction is catalyzed by the
enzyme ornithine transcarbamoylase.
Now, the two reactions
I've talked about here,
the very first feeder reaction and the
ornithine transcarbamoylase reaction
occur in the mitochondrion because
that's where those enzymes are located.
We now have citrulline which is a
molecule that's part of the urea cycle
and we'll follow through the rest
of the reactions of the cycle.
In order for citrulline to react in
the next part of the cycle, however,
it must be moved from the
mitochondria out into the cytoplasm
where the other enzymes of
the urea cycle are found.
Now, the reaction that creates the next
intermediate is catalyzed by the enzyme
argininosuccinate synthetase and creates
the molecule argininosuccinate.
In the process of converting from
citrulline to argininosuccinate,
a transient covalent intermediate
between citrulline and AMP is formed.
That actually occurs before the
argininosuccinate can form.
And it's only after the
aspartic acid is incorporated
into the molecule that the AMP leaves.
So, let's look a little bit more
closely on how that happens.
In this reaction,
we see the intermediate on the side that
has the AMP linked to the citrulline.
That AMP came from the ATP that you see in
the addition reaction immediately above it.
In the next step of the
process, aspartic acid comes in
and displaces the AMP and becomes
linked to the citrulline.
That's what actually creates
In the next reaction, argininosuccinate
is converted into arginine
in a reaction catalyzed by
In the process of making arginine, fumurate
is released from argininosuccinate.
Now, what's happened in this
last set of two reactions?
In the formation of argininosuccinate,
we saw an incorporation of
aspartic acid or aspartate.
In the formation of arginine,
we saw the release of fumurate
So, the net sum of the two of those was
we've incorporated carbons from aspartate.
And amine from an aspartate and we lose
the carbons in the form of a furmurate.
In other words, we
gained an amine.
Argininosuccinate is now carrying
an amine from an amino acid.
You remember that in the urea
cycle we get an ammonium ion
which we've already seen
in the feeder reaction
and now we've incorporated the amine
that we're going to use to make urea.
Well, the next process
actually creates the urea.
Arginine is cleaved by the
enzyme arginase to realease urea
which can then go and be
excreted in the urine
and reproduce the ornithine that was
necessary to continue the reaction
that I've described at
near the very beginning.
In order for that reaction to occur,
ornithine must be transported
back into the mitochondrion.
And we see that transport
process happening right here.