Cholesterol is a molecule, that a lot of people
say "Can’t live with it, can’t live without it".
I hope in this lecture you will
see that the latter is true.
In this lecture I will go through the synthesis
of ketone bodies and cholesterol and
we will see how they are related to each other.
We will talk about cholesterol in health
and also talk about how the
steroids themselves are synthesized
and how bile acids are involved. And these are
all molecules that are related to cholesterol.
Now, in the synthesis of molecules like cholesterol,
we start with a very simple thing.
The simple thing that we start with is
the same thing that we started with
in fatty acids synthesis and that's acetyl-CoA.
In cholesterol synthesis we see
that it's pathway overlaps
with the pathway of making ketone bodies and that's
the first thing that we are gonna talk about.
So in the synthesis of ketone bodies in cholesterol
2 acetyl-CoAs are joined together to make a
4 carbon molecule called acetoacetyl-CoA.
This reaction is catalyzed by the reversal of the
last step of beta oxidation of a fatty acid.
Now you may recall from that presentation
that the enzyme thiolase
catalyzes the breakdown or the cutting
off of two carbon pieces from each
of the fatty acid chains.
When the fatty acid chain has 4, there are 2
molecules of acetyl-CoA that are produced
and if you run that reaction backwards,
the 2 molecules of acetyl-CoA can be made into
the molecule that you see here, acetoacetyl-CoA.
In the next step of the reaction, you
see that 2 more carbons are added
from another acetyl-CoA to make a
6 carbon molecule called HMG-CoA.
This molecule, as we will see, is a branch point between
the synthesis of the ketone bodies and cholesterol.
So we are gonna follow, first of
all, the ketone body synthesis.
Ketone body synthesis occurs in the mitochondrion where is
the cholesterol biosynthesis at least starts in the cytoplasm.