Now to breakdown fatty acids, we go through a process
called beta oxidation, so I wanna steps us through that.
The enzymes forbid oxidation are found
in mitochondria and little organelles called peroxisomes.
This process of breaking down fat generates more
ATP per carbon than sugars do.
Now sugar metabolism is very
important and sugar metabolism is
occurring more readily than fatty acid metabolism is,
partly; because, sugar can travel in the blood
stream more easily than fat and fatty acids can.
Fatty acid metabolism works in
a breakdown process that proceeds
by a chopping off of two carbons
at a time from a fatty acid.
And you can see that happening in this process here.
On the top I have a schematic representation of a fatty acid
and I have marked the two carbon
pieces that get chopped off.
We see first of all, the release of
the fatty acid and the fatty acid is broken
between what are called the α-carbon, as
you can see here, and the β-carbon here.
So in the numbering scheme that's here,
that's between carbons numbers 2 and 3.
So either term is commonly used.
That breakdown process, as I said, releases a
single acetyl-CoA that's a two carbon piece.
And then continues along at two carbons at a time
until the entire fatty acid has been broken down.
Now fatty acid oxidation is a multi-step
process like most metabolic pathways.
But there has to be some processing of the fatty
acids to get them ready for the oxidation.
Fatty acids that start in the
cytoplasm have to first be activated
and then moved into the mitochondrion but, as
we will see that process is a little odd.
The activation of a fatty
acid begins in the cytoplasm.
And this involves the attachment to
the fatty acid of a molecule called
coenzyme A or as people more commonly say CoA.
This is an energy requiring step and
as you can see that ATP energy
is needed to do this and the product of this
is not ADP, as we have seen many times before,
but actually AMP and that's
reflection of the fact
this is a pretty high energy
bond that's being created.
The result of this action is a
molecule called fatty acyl-CoA.
Now fatty acyl-CoA needs to
get into the mitochondrion
where the oxidation occurs. But there
is a little complication with that.
The acyl-CoA won't directly
go into the mitochondrion
so the cell has wasted some
energy, in some thought,
by putting this CoA onto the acyl-CoA
and then we see it gets taken off.
So the next step of the process
starting in the cytoplasm on the left
we see that the acyl-CoA is combined with a molecule
called carnitine to make an acyl-carnitine.
Now this step is essential for the movement
of the acyl-group into the mitochondrion.
And the reason is, is that CoA just can't
make that move across the lipid bilayer.
I should also mention that we are
looking at the mitochondrion here.
So on the right side, where it says the MATRIX, we are
talking about the inside of the mitochondrion,
and of course, on the left side where it says CYTOSOL
we are talking about the cytoplasm of the cell.
In between the two you see the yellow
and blue lines that are drawn there
and those relate to two layers of
membrane covering the mitochondrion.
The yellow one being what's called the outer
layer and blue one what's the inner layer.
The blue one is very impermeable to a lot of substances
whereas the yellow one is fairly permeable.
So you see the acyl-carnitine moving into what's called the
intermembrane space, the space between the yellow and blue lines,
and then when it gets there it encounters
the yellow protein there that is a transfer
protein that physically moves the acyl-carnitine
into the mitochondrion matrix, as you see.
Now once it gets to the mitochondrion then the
reverse of all of this process actually happens.
The CoA that was floating around the mitochondrion
is now attached to the acyl group
and the carnitine is released.
The carnitine ultimately makes it back out
into the cytoplasm and the process continues.
So what we done here is that we
described here as a shuttle. The shuttle
has carried acyl group from the
cytoplasm into the mitochondrion.
We have an acyl-CoA in there and the acyl-CoA
is the target for the oxidation.
Beta oxidation proceeds now
starting with that acyl-CoA.
So we see now the step by step process
where by a fatty acid is oxidized.
The oxidation in this process is
shown in the first step below.
We see an enzyme called
and it does the very first
reaction on that fatty acid.
You can see that all the action in
fatty acid oxidation occurs between
carbons 2 and 3 or the α and β
depending upon how you call it.
The first oxidation is removal
of electrons and protons
and those are donated to FAD to make FADH2.
The result of that oxidation creates
a trans bonded fatty acid called
trans delta 2 Enoyl-CoA. That name
isn't very commonly used by the way.
But the important thing
is the trans fatty acid
and I note that it's really relate
to trans fat. Trans fat happens
or is made for other reasons. This is a normal
intermediate in fatty acid degradation.
Trans fat is typically made by
chemical treatment of food.
Now there are three forms of this enzyme. There
is a form that works on long fatty acids,
typically longer than about
20 or so. A form that works on
medium size fatty acids between
about 18 and 10 carbons.
And then there is a form that works on short
fatty acids typically less than 10 carbons.
Now of note the acyl-CoA-dehydrogenase that
works on the medium form of the acid
is a form that is absent in infants
who have died from sudden
infant death syndrome.
Now it's not a cause-effect but there appears to be a relationship
between the absence of this enzyme and SIDS.
Now the FADH2 that was
generated in this process
can be taken into oxidative phosphorylation
and used to make ATP.
So we are seeing at these oxidative processes are used to
generate energy that a cell can use for other purposes.
Now in the second reaction of
fatty acid oxidation we see
that this trans intermediate
gets a water added across it.
This is a very common reaction
in organic chemistry,
and it's catalyzed by the
creates a molecule that has a hydroxyl group
on the beta, carbon or carbon number 3,
and that hydroxyl group is in the
L configuration, as you can see here.
Now this reaction is similar to a reaction that
occurs in the citric acid cycle. In fact
this reaction and the next two reactions are
very similar to citric acid cycle reactions.
And this allows for a oxidation
that will occur in the next step.
So the second oxidation of fatty acyl-CoAs
occurs by the process that you can see here.
On the bottom you see that we have the hydroxyl
fatty acid that we created on the last step
and on this step we see that the hydroxyl
group is converted into a ketone.
That oxidation is catalyzed by the
enzyme that you see on the screen
and causes production of NADH plus H+.
That is the transfer of electrons and
protons, as we have seen before.
Now this reaction is similar to
the malate dehydrogenase reaction
of the citric acid cycle. This
reaction is preparing us for the final
step in which we will actually
cleave the fatty acid into two pieces.
The NADH, of course, like the FADH2,
can be used to generate ATP
and oxidative phosphorylation.
Now on the last step of the
process we see the keto of
acyl-CoA that was created in the last step of
the process being broken into two pieces.
So the bond between carbons 2 and 3
or the α and β, as you can see here,
is broken and the product of that is an acyl-CoA that
is being shorten by two carbons and an acetyl-CoA.
Now the acetyl-CoA itself can be targeted for
additional oxidation in the citric acid cycle.
If we look at the oxidation, for example, of
the fatty acid palmitate which has 16 carbons,
the complete oxidation of that fatty acid
can generate close to a 140 ATPs.
So fatty acids have a lot of
energy stored with inside of them.
Now the thiolase enzyme that
catalyzes this reaction is interesting;
because, obviously it is catalyzing this breakdown.
But also the reverse reaction of this
creates an important intermediate if
the acyl-CoA only has 2 carbons.
So if we have an acyl-CoA that only has two carbons,
on the right side, then we can
combine that with the acetyl-CoA
Well an acyl-CoA that contains 2 carbon is
also acetyl-CoA. So what thiolase does
is it can take two acetyl-CoAs and
make a four carbon intermediate.
Now as we will see later that's
an important consideration
for making lipids called ketone bodies.