In this lecture, we’ll focus on two of the
fat-soluble vitamins, vitamins K and E.
And twp groups of molecules involved
that what we call one-carbon metabolism,
vitamin B12 and another group of
molecules called the folates.
Now, vitamin K is a fat-soluble vitamin
that plays very important roles
in the blood clotting process and also an
important role in maintaining bone health.
Like the other fat-soluble vitamins,
vitamin K is stored in fat tissue.
It is found very abundantly in green leafy
vegetables like kale, spinach and collards.
It’s a compound that’s
stable in the air,
but it does decompose
when exposed to sunlight.
There are several forms of vitamin K including
natural forms that are found in nature
and man-made forms that also appear
to function in a similar fashion.
Vitamin K-related modifications facilitate
the binding of calcium to target proteins.
And this is what really vitamin K’s function
is in both the blood clotting process
as well as in maintaining
It’s the absence of vitamin K that leads
to uncontrolled bleeding in an individual.
Meaning of course that vitamin K is
essential for the clotting process.
A deficiency of vitamin K, however,
is relatively rare in healthy adults.
And it is required for
Vitamin K is actually
a group of molecules.
Now, the form known as vitamin K1
is also known as phylloquinone.
It’s an electron acceptor
that is found in plants
in the photosynthesis system
known as photosystem I.
As I said, it’s found
in the green leaves
and because of the chlorophyll
that the plants have,
this compound is quite
abundant in those plants.
Vitamin K is involved in carboxylation.
It is adding carboxyl group
to the glutamates side chains
of the blood clotting factors.
This includes blood clotting
factors II, VII, IX and X.
Vitamin K can also be involved in the
carboxylation of other compounds,
in the preventing a clotting process
as well as some proteins.
So some of the anticoagulation factors
that a vitamin K can carboxylate
includes the glutamate side chains
of factors protein C and S.
So we can imagine that vitamin K’s role
of carboxylation is very important one.
And we will see in a minute
why that is the case.
So as I said, vitamin K
is a group of molecules.
Vitamin K2 is known as menaquinone
and is a group of compounds that differ in
a number of isoprene units that they have.
An isoprene unit is a group
of carbons and hydrogens
that are shown in the figure on the
right in the bracketed portion.
They actually contain five carbons
and the rest being hydrogens.
The isoprene unit is the way
that the molecule is built.
So molecules that are built using
this vary in how many they have
and therefore vary in their sizes
according to five carbon units.
MK-4 also known as menatetrenone and
MK-7 are subtypes of vitamin K2.
They are also involved in
glutamate carboxylations as is K1
and they're involved at the
same level as vitamin K1 is.
Vitamin K1, as I said,
is found in plants.
But bacteria take that vitamin
K1 that we get in our diet
and they convert vitamin K1 to vitamin K2
and another form known as MK-7 as
well as MK-8, MK-9, MK-10 and MK-11.
So you see that there are quite a variety
of these K’s that are present in our body.
MK-4 also known as menatetrenone
can be produced by animals in their
testes, pancreas and arteries.
And it turns that it’s the only form
of K2 that is actually made by animals.
So we see that bacteria
play a very important role
in us being able to have the right
vitamin K that we need in our body
and they do this through
metabolism residing in our gut.
So these are three synthetic forms of
vitamin K that you can see on the screen
that are man-made, but they all will also
function in the capacity of vitamin K.
This includes vitamin K3 (menadione),
vitamin K4 is shown here and vitamin K5.
And all of these appear
to be pretty fairly safe
with the exception of vitamin K3
which in higher doses can be toxic.
Vitamin K, as I said, is needed
for carboxylation of proteins.
So let’s take a minute to
understand how that happens.
Here is the amino acid glutamate which
is found within a polypeptide chain.
We can see its side chain that
contains the carboxyl group
at the very top
of this molecule.
Catalysis by the enzyme glutamate
carboxylase using oxygen,
carbon dioxide, water and protons
produces a modified form of glutamate
known as gamma carboxyglutamate.
This gamma carboxyglutamate has an extra
carboxyl group that is added to it.
And that turns out to be critical
for the function of this protein
because with this added carboxyl
group, the molecule can bind calcium.
Now, calcium, as we’ve seen over
and over in these lectures,
is very important for a
variety of processes.
And in the blood clotting process, calcium
is abundant at the place of the clot.
So the ability of blood clotting
proteins to bind to calcium
helps them to remain at
the site of the wound
to help the clotting process to occur.
The way that vitamin K fits into the scheme
is vitamin K is a co-factor for
the glutamate carboxylase.
This co-factor allows glutamate
carboxylase to do what it does.
In the reaction that’s catalyzed
by putting the hydroxyl group on,
this is a very unusual reaction
again using molecular oxygen.
Vitamin K acts as an acceptor
of one of the atoms of oxygen.
So you can see that vitamin
K in this reaction
is converted to an unusual
molecule called vitamin K epoxide.
And that oxygen, that vitamin
K accepted from the oxygen,
is pressed in a three-membered triangular
ring on the right side of the molecule.
In order for the vitamin K
to function in the body,
it has to be reconverted back to
its original form by an enzyme.
If that reconversion
back doesn’t occur,
then the body will eventually
run out of vitamin K
and the person will lose
the ability to clot blood.
So the recycling process,
vitamin K epoxide
molecule is very critical.
Recycling is essential for the body to
have the clotting factors that it needs.
Well, the reaction that needs to happen
is actually a fairly simple one,
although it’s kind of odd.
It involves the loss of water from
vitamin K epoxide as the reaction shows
and that involves the
removal of two hydrogens
from the two carbons
attached to the oxygen.
And those two carbons bind to the
oxygen itself producing water.
That results in the
reproduction of vitamin K.
This reaction is catalyzed
by a very important enzyme
known as vitamin K
Now, vitamin K epoxide reductase is
present in normal amounts in the cells
and this reaction occurs pretty
routinely and you don’t think about it.
But there are people, for example,
who have problems with clotting.
Those people who have problems
with clotting may lose a limb.
They may have problems with
heart attacks or stroke.
And it’s known it is fairly easy to
measure a person’s clotting ability,
how clotting tendencies that
a given person’s blood has.
If you’re a person who
has blood that tends to
clot more readily or
form clots more readily,
your doctor may put you on
what’s known as a blood thinner.
And blood thinner is a molecule
that inhibits this reaction.
One of the blood thinners that is
commonly used is known as warfarin
or also called Coumadin.
Warfarin is also known rat poison.
So some of the people that you know
who take blood thinning medications
are actually taking a form of rat poison.
Well, they're not getting
poisoned of course
because a person who was given this
as a treatment by their doctor
is given it in limited dose.
So it takes a certain
amount of warfarin
to reduce the clotting to a
level that is acceptable.
Too much warfarin, you can imagine,
will result in too little clotting.
When you have too little clotting,
you can die of hemorrhage.
So getting the right level
of clotting is important
and warfarin can play
a very important role
in establishing the right
level within a person.
Once the person is on warfarin, they will
periodically have to go to their doctor
to get tested regularly to see if
their clotting tendency has changed.
And then the amount of warfarin that they’re
given will be adjusted accordingly.
Warfarin blocks vitamin
K cycling, as I said.
The lack of vitamin K stops
And that protein carboxylation is
critical for the clotting process.
And low protein carboxylation
can slow the blood clotting.
Vitamin K is also important
for bone health.
It stimulates the carboxylation of bone
proteins and activates many of them.
And this turns out to be
important because we remember
that bones are abundant
source of calcium.
Three of the proteins that vitamin
K carboxylates are shown below.
The first is osteocalcin.
It binds to the bone matrix
and stimulates osteoblasts.
And it does this of course
by binding that calcium.
If it gets carboxylated by
vitamin K appropriately,
then that binding will occur and the
bone matrix will be stimulated.
The matrix gla or gla
protein also binds calcium
and it organizes bone tissue
in the proper fashion.
And the last is periostin
and it’s involved in the cell
migration during bone development
and maybe overexpressed
in some cancers.