That next amino acid we consider
in biosynthesis is that a proline.
Proline is made in a relatively simple fashion
in three steps starting from glutamate.
The first step involves
the synthesis of
which I don't show here.
The first step beyond that then is the
phosphorylation of the glumate-5-semialdehyde.
That oxidation and
dephosphorylation is necessary
to produce the cyclization
And that's what we see
on the screen below.
The cyclization that happens
is spontaneous and does
not require an enzyme.
We can see that cyclization
to make one
Cyclization happens without any other
thing being present in the reaction.
The last step that one
pyrroline-5-carboxylic acid gets reduced
and the reduction of that
produces the amino acid proline.
Arginine is an amino acid that
can be made in multiple ways.
In arginine, as we will see
in the urea cycle, is a very
important sort of central enzyme
for doing a variety of things.
So there four ways to make
arginine and I'll describe them
right here and then show you
later how those reactions occur.
The first is a forward
reaction that takes two steps
coming from citrulline
and ATP and aspartate.
That process occurs in the urea cycle in
the normal direction of the urea cycle.
The second way of making
arginine is production
from asymmetric dimethyl
arginine or ADMA.
This is a modified form of
arginine that's found in proteins.
It differs from arginine
in having a metal group
and that metal group is put on to
arginine after the protein is made.
To get ADMA, one has to
break a protein down
by using proteolysis and
then ADMA is released.
So, ADMA is made into arginine after
a protein has been broken down.
The third reaction for making
arginine involves a reversal
of a reaction of the urea cycle
using the enzyme arginase.
This reaction involves the
molecule known as ornithine
and we'll see how that
actually is produced.
The last way of making arginine is a
reaction that involves nitric acid.
This is reaction that is actually
used to make nitric acid
in cells and it involves
citrulline, nitric acid, and NADP.
So arginine is a central
part of the urea cycle.
And remember that the function of
the urea cycle is to produce urea
for excretion because excess
amines are problematic.
The cell has to be able to have
arginine in order to do that.
The ADMA reaction that actually
goes backwards to produce
arginine interferes with the
production of nitric oxide.
Nitric oxide is a very important
signaling molecule that cells use.
So again, cells have to balance need
for one molecule versus need for
another in considering which pathway
is used to make a molecule.
Arginine may play role in very important
diseases involving cardiovascular disease,
diabetes mellitus, erectile
dysfunction and kidney disease.
So it's a very
important amino acid.
Deficiency of the enzyme arginase
is another important reaction to
consider because it leads to the
genetic disease known as argininemia.
And argininemia as we will see for
other amino acids involves the
accumulation of arginine and more
importantly ammonium ions in the blood.
Thos ammonium ions as we
can describe are toxic.
Well, in this set of slides, I want
to show now the reactions that
I've just described previously the
four ways of making arginine.
We see arginine in the lower part
of the screen and we see how
it connects to these molecules
that I've been describing.
We start with reaction number one which
involved the production of arginine
from citrulline reaction -- set of
reactions that occurs in the urea cycle.
There are two steps
as I've described.
The first step being a
very energy-intensive step
that involves the cleavage of ATP to make
AMP plus two inorganic phosphate ions.
This reaction is central
to making arginine in the
urea cycle but it's a very
So cells again, are cautious in
how much they use to do this.
In each of the reaction
that I show here,
the green arrows point in the
direction of making arginine.
And we see that each reaction is
reversible so there's an arrow
pointing the other direction that
can go on different circumstances.
is a product of the
first reaction is converted
into arginine in
the next step, and we can see that was the
product of arginine for pathway number 1.
ADMA after approaching
has been broken down
can be demethylated to make
arginine as we have seen.
And we also see that by starting
with ornithine and urea and
going upwards with the lost of
water, we can make arginine.
Now, normally, this reaction
as it occurs in the urea cycle
involves the downward direction.
So, in order to make arginine, we have
to actually reverse that reaction.
Normally, that's not a very
common way of making arginine.
The last way of making arginine is also
a reversal of a reaction that occurs in
the cells and this involves the nitric
acid signaling that I've described before.
If we make arginine using this
pathway, we use nitric oxide.
And nitric oxide, as I said, is an
important molecule for signaling.
So, cells are careful again
in how much this reaction is
moved to the right versus how
much it's moved to the left.
This reaction is an oxidation
and we can see the oxidation
occurring as a result of the
NAPD being converted into NAPDH.