So I've now gone through
the cycle as a whole.
What I want to do now is focus
in a little bit more closely
on each of the enzymes that
I've been talking about.
The first enzyme of course is
carbamoyl phosphate synthetase.
Now, this reaction requires ammonium ion.
And the ammonium ion in this reaction
is ultimately coming from
glutamine or glutamate.
These may have gotten their
ammine from another amino acid.
The reaction requires the
action of either glutaminase
in the case of breaking down
glutamine to make ammonium ion
or glutamate dehydrogenase which breaks
down glutamate to get that ammonium ion.
We see these reactions here.
It's a hydrolysis in the case of glutamine
to release and produce glutamate
plus that ammonium,
or it's also hydrolysis in the case of
glutamate that produces alpha-ketoglutarate
and the ammonium ion as we see here.
In the case of the glutamate
dehydrogenase that's an oxidation
as the name dehydrogenase
and the electrons are donated
to NADP to make NAPH.
So, we have produced the
ammonia or ammonium
ion necessary for the
reaction I've described.
The production of the bicarbonate
is done very easily within the cell
and I won't go into
that right here.
We thus have the bicarbonate
and the ammonium that we need
for the reaction catalyzed by the
carbamoyl of phosphate synthethase
and we see that happening right here
coming either from the glutamine side
or from the glutamate side.
The net result is that we have
made the carbamoyl phosphate
necessary for the
The ornithine transcarbamoylase
reaction is shown here.
In this reaction, we see of
course carbomyl phosphate
combines with ornithine to make citrulline
with the release of a phosphate.
The enzyme is of course
The enzyme is expressed only in the
liver, no other place in the body.
It is the most commonly deficient
enzyme that occurs in the urea cycle.
And I'll take later about
how deficiencies of
enzymes in the urea cycle
relate to human disease.
The reason it's the
most commonly deficient
enzyme is that it's an
It's found in the X chromosome
which means that males are much more likely
to suffer this deficiency than females.
In severe deficiency,
ammonia levels can rise
to very lethal levels
if it's left untreated.
And the way that this is treated
is commonly with liver transplant
or very low protein diets to keep the
ammonia levels from becoming high.
In the production of citrulline, there
are other ways that this can happen.
So we saw one way that it happened
earlier in the urea cycle
but it can be made by
And that other mechanism involves
the enzyme nitric oxide synthase.
This reaction is shown here and
it starts actually with arginine.
It involves the reduction of arginine
and the combining of four
molecules of oxygen.
This s a very complicated reaction
catalyzed by the enzyme
nitric oxide synthase.
The product of this reaction
is two citrullines,
two nitric oxides,
water, and NADP.
The advantage here is that cells can use
this as a way of making nitric oxide
which is an important molecule in signaling
and can also provide
an alternate means
of making citrulline that can
be used in the urea cycle.
This, therefore, by passes the mitochondrial
part of the urea cycle if necessary
and at the same time
produces nitric oxide.
Arginine is a substrate for this reaction
and the use of arginine can
be taking away arginine
from the urea cycle
if that happens.
The nitric oxides system, as I
said, is important for signaling
and so this is an important consideration
as nitric oxide is needed.
Nitric oxide helps
which is the lowering
of the blood pressure.
Now, the citrulline gets
transported to the cytoplasm
if we are still in the urea
cycle as I want to follow here.
The movement of citrulline
to the cytoplasm
requires an ornithine-citrulline
That is an enzyme that's embedded in the
inner membrane of the mitochondrion.
That is called
because the two
molecules are swapped.
Citrulline is moved out of the mitochondrion
at the same as ornithine is moved in.
And we'll see that's important
at the end of the cycle as well.
The enzyme is an antiport,
as I said, moving citrulline
out and moving ornithine in.
The transport protein is needed
for both parts of the urea cycle.
So, an absence of this from the
mitochondrium has very severe consequences
a person could not run the urea cycle.
A deficiency that tanslocase mimics
many of the other enzyme deficiencies
that we see in the urea
cycle particularly that
of a defective or deficient
Now, this condition at birth can be more
serious that it's onset in adulthood.
During the development of the brain,
the toxic ammonia needs to be
release and needs to be removed.
And so, if the urea cycle cannot
run, then there are problems.
Adult onset conditions are
working with an existing brain
and don't have such