Vitamin B12 is by contrast of vitamin
that’s very unusual in its structure.
You can see one of the forms of
vitamin B12 on the screen here.
And it participates in a very
unusual set of reactions.
Now, it turns out that these unusual
reactions that it participates in
and that it helps to contribute
to are very critical.
Absence of vitamin B12 results
in various health issues.
Cyanocobalamin is one of
the forms of vitamin B12
that is made and you can see
them on the screen here.
An artificial form is made by human beings,
but given the people who lack vitamin B12.
And It functions
perfectly as vitamin B12
and there are various forms of vitamin
B12 that are naturally produced as well.
Now, one of the critical things about vitamin
B12 is that it’s not made in plants.
So people who are one on strict vegan diets,
who are not eating any animal products
will become deficient
overtime with vitamin B12
because they can’t get what
they need from plants.
People who are on diets like that need
to be sure they check with their doctor
and get supplements as appropriate
to get enough vitamin B12
to maintain the reactions
we’ll describe here.
Vitamin B12 is normally obtained in
a diet from meat and dairy products
or other animal products
and it doesn’t take a lot.
Deficiency of vitamin B12 leads
to pernicious anemia which is
a very severe anemia relating
to your blood supply.
And people who
sometimes lack energy,
one of the things they'll check in a person
is whether vitamin B12 level's okay.
Because people with vitamin B12
deficiency will first notice
that they don’t have energy
because of lack of that vitamin.
There are several different
forms of vitamin B12 as I said.
Methylcobalamin is found
in the cytosol of cells.
Adenosylcobalamin which is a
form of cobalamin in which
the adenosyl group of ATP is linked to
cobalamin is found in the mitochondria.
And the bioactive forms
of vitamin D are needed
for the metabolism
of a few compounds.
One is the synthesis of methionine.
The second is handling propionic
acid which is present in our cells.
And third is for the formation
Now, I want to show you here the
reaction where vitamin B12 is necessary
for the metabolism of an unusual
compound called propionic acid.
Vitamin B12 is important
because what it does
is it allows the cell to be able to break
difficult to break
single carbon bonds
and move that carbon from
one position to another.
And the reaction I’m going to show
you here is a pretty unusual one.
In the set of reactions
that you can see here,
propionyl CoA on the left
is a three-carbon molecule.
It is being converted into a 4-carbon
molecule on the right known as succinyl CoA.
Succinyl CoA is a metabolite
in the citric acid cycle.
So the goal is getting from
this 3-carbon propionyl CoA
to the 4-carbon succinyl CoA and the
cell goes about it in an unusual way.
The first step in the process
is to add a carboxyl group
from carbon dioxide using
propionyl CoA carboxylase.
That is the enzyme that
catalyzes the first reaction
and it puts that carboxyl group
that you can see in the square
on the central carbon of that three-carbon
propionyl CoA making methylmalonyl CoA.
Well, methylmalonyl CoA cannot
be metabolized as such.
That molecule has to be rearranged
before it can become succinyl CoA
and that rearrangement uses an enzyme
known methylmalonyl CoA mutase
that requires vitamin B12.
And that reaction itself is unusual
because that carboxyl group
is in the wrong stereolized
numeric configuration to start.
It has to be moved essentially from
the right side of the molecule
to the left side of the molecule
and then that carboxyl group
has to be moved to the top
to get to where it is
in the succinyl CoA.
Vitamin B12 is critical for that feature
because vitamin B12, as I said earlier, can
break those carbon-carbon double bonds
and move things around.
Vitamin B12 is also important in the
sense that has an atom of cobalt in.
It is the only compound in our
body that contains cobalt.
And that cobalt is important
for that function to hold onto
the carboxyl group in this
moving around process.
So vitamin B12 is important for the
synthesis of methionine from aspartic acid.
If you remember from the amino
acid metabolism lecture,
methionine is in the aspartic
acid family of compounds.
So we can start with the aspartic acid
and get all through to methionine
and the very last reaction of that
process requires vitamin B12.
Let’s take a look at the reactions occurring
to go from aspartate to methionine.
The first step of aspartate
producing the aspartyl beta
phosphate as you can see here.
Reduction of that produces beta aspartate
semialdehyde as you can see,
followed by another reduction to
produce the intermediate shown
in the central part
of this figure.
At that point, an unusual addition
is made and that succinyl CoA
is joined to this molecule to
make an even bigger molecule.
In the next reaction,
cysteine replaces the succinate that
had been added into the last molecule.
Now this turns out to be
an important reaction
because cysteine is a source of
sulfur for making methionine.
Cysteine and methionine are the only
two amino acids that contain sulfur.
So the sulfur source is essential
for making methionine.
That creates the compound known as
cystathionine as you can see here.
We’re getting very close
to having methionine.
Breakdown of cystathionine
yields three products.
Pyruvate as you can on the top
and ammonium ion which is involved in the
loss of the amino acid in the process
and finally homocysteine as
you can see on the right.
This reaction, I’m showing some
detailing because it’s the reaction
that requires vitamin B12 in
the synthesis of methionine.
It also requires interaction
of two folates.
The folates are the source
of the extra carbon
that is added during
the synthesis process.
So the carbon source
for the extra carbon,
this methyl group that's being added,
is N5 methyltetrahydrofolate.
Folates are involved in one carbon
metabolism just like vitamin B12 is.
But vitamin B12 is involved
in handling those carbons
and the folates are
sources of the carbons.
So the source here is as noted.
The enzyme performing this catalysis
requires B12 as coenzyme.
Without B12, this reaction cannot
occur and we can’t make methionine.