Nitrogen as I said earlier in
this lecture is problematic
when it’s converted into forms
that are very, very reactive.
Those reactive forms of nitrogen are
known as reactive nitrogen species
and they’re kind of paired
with reactive oxygen species.
In either case, we have typically
molecules that can readily form radicals.
And as a result of the
formation of those radicals,
it can rapidly combine undesirably
with other molecules in the body.
Now, this slide shows the
production and reactions
of several reactive
I’m not going to go through all of them,
but I’m going to point out the highlights
and the important parts of
each one for consideration.
In the synthesis of nitric oxide,
for example, nitric oxide
actually is a radical.
And so, our body is actually
making this for one purpose,
but the down side of the nitric oxide,
it can combine with other things.
That’s the NO that we see in reaction one.
Nitric oxide can combine
with other molecules
such as the NO2 shown here
at the nitrous compound.
Combining these two molecules together
creates dinitrogen trioxide, N2O3.
That molecule is very reactive.
You see it can combine there
with thiols to make this RS
as the S part being the thiol part and
the NO being the nitrous oxide part.
N2O3 is very active in the
process of nitrosation.
That is adding a nitrate
to something else.
And that is a very big problem associated
with these reactive nitrogen compounds.
We see in the figure on the right
some of that nitrosation happening.
Now, nitrosation can cause problems,
because if the nitrate, for
example, adds to an animo acid,
the nitrate is negatively charged
and will change the properties of
protein that it gets linked to.
Well, changing properties of
proteins is not very good.
We recalled it, for example, phosphorylation
change a signaling molecule
into a non-signaling molecule or a non-signaling
molecule into a signaling molecule.
When cells lose control of their protein
in this way, major problems can result.
In the third reaction,
nitroxide combines with another
reactive molecule called “superoxide”
to make a very reactive molecule
known as peroxynitrite.
We see the arrow indicating peroxynitric
and participate in oxidation.
And we’ll see in the next slide,
peroxynitrite can combine with several
things to cause major problems in the cell.
The other reactions that are shown in the
very bottom involve manipulations of iron
involving reactive nitrogen species,
converting iron from +2
to +3 or +3 to plus +2.
Each of those can create
problems and create themselves
reactive oxygen species where not desired.
Now, the most potent reactive nitrogen species
that I’ve shown above is peroxynitrite.
So let’s talk a little bit more
about it on the next slide.
Peroxynitrite is formed, as I said,
from nitric oxide in superoxide.
And you can see the reaction
a little better here.
The peroxynitrite ion that’s
made can readily react with DNA
and with proteins causing damage.
We know that reacting with DNA
is going to result in mutation.
And we know that reactive with protein
is going to cause damage to the protein
and may change the function
of the protein as well.
The part of the protein that
most commonly gets oxidized
by peroxynitrite is the
side chains of cysteine.
Cysteine, you recall, has
hydro groups, sulfur.
These are very reactive
particularly with peroxynitrite.
Another amino acid to which peroxynitrite
can react is that of tyrosine side chains.
Now, you remember from the discussion of
signaling in another one of these lectures,
that tyrosine side chains
are very important
phosphorylation targets in
the process of signaling.
If those side chains are altered,
we may very well result in
alteration of signaling processes
and signaling process
alterations can lead to cancer.
Peroxynitrite can also react with
transition metal such as the iron,
in hemoglobin, myoglobin,
And we know the importance of all those
molecules in the carrying of oxygen
and in the electron
Well, the three reactions on
the right part of the screen
show some of the other types of reactions
that peroxynitrite can be involved in.
I’m not going to
go through them.
But I will point out that every
place in those reactions,
where you see a molecule produced
that has a single dot beside it,
it’s a radical
and radicals can be combined with other
biochemicals at random causing problems.
So we see the peroxynitrite can, in fact,
create enormous problems for cells
and increase the number of reactive molecules
every time they react significantly.
Well, this reaction in these lectures,
I’ve gone through the ways in which
the ammonium and the amines
produced by amino acid catabolism
are handled by the body and used
to create urea for excretion.
I’ve also talked about the
reactive nitrogen species
that can be created as a result of nitric
oxide in other types of nitrogen compounds.
The results of these are very
hazardous for the human body.