It's safe to say that without a
lipid bilayer, a cell is not a cell.
In this lecture, I will cover the metabolism
of the primary molecules involved in making up
the lipid bilayer of the cell membrane.
This will include a discussion
of the glycerophospholipids
and also the synthesis of the sphingolipids.
Now the glycerophospholipids are, as I said,
one of the major components of the cell membrane.
You can see how they come about
or how their name comes about
by virtue of the fact that in the middle, as
you see here, they have a glycerol backbone.
On the right side, they have a phospho component
containing phosphate that is very polar.
And on the left they contain the lipid part
of the glycerophospholipids which are
two fatty acids attached to the glycero.
Now this compound is very amphiphilic meaning
that it has a portion of it that is very polar
and another portion of it that's non-polar.
Now this schematic structure of a glycerophospholipid
that I show on the screen here
I would carry forward into the next slide.
Please note the "X" at the lower right;
because, this is the point of attachment
for other molecules to make the
Now you can see on the right, that
schematic structure, and you can see the X
in the box that I have indicated here.
If the X is a hydrogen then the molecule that
we are talking about is phosphatidic acid.
Now phosphatidic acid is not a significant
component of the lipid bilayer.
But it actually is a precursor for the
synthesis of the other molecules below.
If X is a serine, as you can see here
then the compound that results is phosphatidylserine,
serine of course is an amino acid.
If the X is an ethanolamine we
have a phosphatidylethanolamine.
If the X is a choline, we
have a phosphatidylcholine.
And finally if the X is inositol
we have a phosphatidylinositol.
Now in contrast to the other additions
that were above phosphatidylinositol,
the inositol itself does not ionize
but it is a very polar compound,
thanks to the hydroxyl groups that are on it.
Glycerophospholipids synthesis overlaps
the synthesis of fats, as we shall see.
Now the starting point for both fats and
glycerophospholipids is the molecule you
see on the screen, glycerol-3-phosphate.
is added a fatty acid
in an ester bond at position 1
by the enzyme acyltransferase 1 as you can see.
We saw this also in fat synthesis
to create lysophosphatidic acid.
The lysophosphatidic acid gains
a fatty acid on the
second carbon of the glycerol just
like fat synthesis to create
the phosphatidic acid that
we are already talking about.
Now you can see the phosphatidic acid
at the very top of the structure
and that is just mearing what we
brought into this original structure.
The synthesis of additional phosphatidyl compounds
now can proceed by two different mechanisms
and these are very general
in nature as you will see.
Both mechanisms involve the use of
what's called an activated intermediate.
An activated intermediate is a
molecule that has a high energy bond
that uses the energy of that bond to donate
a part of itself to something else as we shall see.
Now the two general mechanisms you will see have
some parallel, although, they sort of flip things around.
The first method I will show you is
starting with a molecule that is activated
through the phosphatidyl compound.
Now this material is called CDP-diacylglycerol.
The CDP portion of this molecule, of course, comes
from the nucleotide CTP which is used in the synthesis of RNA.
And the rest of this is the phosphatidic acid that
we had synthesized as of the last image on the screen.
So if we take phosphatidic acid and combine
it with CTP, we make this molecule.
We split out in the process a
pyrophosphate that's the PPi on the side.
We started with 4 phosphates, one on phosphatidic acid
and three on CTP. We end up with 4 phosphates.
Two in the CDP-diacylglycerol and two in the pyrophosphate.
Now the phosphatidyl portion is shown here
again for your orientation; because, that's the part
that will be carried forward into the
synthesis of the phosphatidyl compound.
The CTP splits off not as
CDP but rather as CMP.
So it leaves behind one of its phosphates
to the phosphatidyl compound.
Okay, we can see a reaction here for example with inositol.
CDP-diacylglycerol plus inositol yields phosphatidylinositol
plus the CMP, that I said will split off.
Now this reaction requires the energy of that high energy
bond of the activated intermediate of CDP-diacylglycerol.
Thanks to the energy of that bond, the two
molecules can be joined together that is the
phosphatidyl compound and the inositol.
This reaction does not
require energy from ATP;
because, the energy comes from the activated
intermediate that was created previously.
Now the second mechanism for the
synthesis of glycerophospholipids
sort of flips around that use of the activated
intermediate, as we shall see.
So, first of all, here is a compound that
we wanna add to the phosphatidyl part
as an X on the figure on the
upper right. This is ethanolamine.
In order to do this is what we do is
we activate ethanolamine using the CDP.
Now before we activated the
phosphatidyl compound with the CDP.
In order to active the ethanolamine we
first put a phosphate onto it to
make phosphorylethanolamine. Now
is a substrate for making CDP-ethanolamine. Now
the way this is occurring is, of course, we
have one phosphate on the phosphorylethanolamine.
We have three phosphates on the CTP
and when we will combine the two
what we end up with is CDP-ethanolamine
and we split out pyrophosphate just
like we did in the phosphatidyl material.
This CDP-ethanolamine is also
an activated intermediate.
So now the energy for creating the joined compound
is going to come from this activated intermediate.
So we see during the process of
this activation that the CMP
will split off exactly like we saw the CMP
split off of phosphatidic acid earlier.
The ethanolamine, meanwhile, will add
two what would be diacylglycerol, as we should
see, to make the phosphatidyl compound.
So here is the CDP-ethanolamine here.
Here is diacylglycerol. Now this is not
phosphatidic acid in this case but rather
is a phosphatidic acid minus the phosphate;
because, the phosphate here is coming
from the activated intermediate.
When we put these two together we
and CMP. So we have split off
the CMP and once again
we came in with two phosphate on
the activated intermediate.
One of them, got carried forward into making
the final phosphatidylethanolamine.
So these two mechanisms that I have described,
either activating the phosphatidic acid or
activating the molecule added to it
are general ways in which glycerophospholipids
are synthesized in cells.