Now, vitamin D is unusual
in another respect.
Vitamin D acts like
a hormone as I said
and it is in fact a steroid hormone
as some people categorize it.
However, steroid hormones move
across cellular membranes at will.
They don’t have to be transported.
Vitamin D, however, has a receptor
protein on the cell surface
that binds to it and
brings it into the cell.
This is unusual for
a steroid hormone.
Vitamin D bound to the vitamin D
receptor then interacts with a protein
inside the cell known as the
vitamin D receptor or the VDR.
The VDR is similar to the
steroid hormone receptors,
but in the case of the VDR, the
vitamin D is actually brought to it
by the vitamin D binding protein
on the surface of the cell.
Vitamin D-VDR complex then
goes into the nucleus
and binds to hormone response elements
or HREs as they're called in DNA.
The effect of this vitamin D-VDR
complex binding to these elements
causes genes associated with those
elements to be expressed and made.
So what we can see as
happening here is vitamin D
is actually affecting gene
expression inside of a cell
as a result of movement into the cell
and ultimately into the nucleus.
Vitamin D, of course, control the
transcription of specific genes
and it does with the process that
I have just described to you.
What are these genes?
Well, the genes are involved in
mineral metabolism as we have seen.
And they’re also involved
in immune functions
that help provide for a strong
and healthy immune system.
This is a different function of vitamin D
than what I’ve talked about up to this point.
Vitamin D can also interfere with
receptor tyrosine kinase signaling.
As I’ve talked about in another lecture,
receptor tyrosine kinase
signaling is very important
in the process of controlling
Because of this, vitamin D
It slows the division process down
and allow cells to differentiate.
It also favors the process of
apoptosis or programmed cell death,
in which cells that have gotten out of
whack automatically commits suicide.
For this reason, vitamin
D is actually important
in anti-tumor properties
as we can see.
Vitamin D also inhibits the
process of angiogenesis.
Angiogenesis is the process whereby
new blood vessels are made.
Now, new blood vessels
are made by some cells
that are stimulated by the
production of tumor cells.
If we inhibit the production of angiogenesis,
we inhibit the production of tumors
and so again, vitamin D has anti-tumor
properties that help to keep us healthy.
Now, calcium, as I said, inside
this cell has many functions
and the cell is very
careful with it.
For one, it is a second messenger.
We’ve talked about second
messenger in another lecture.
The second messengers
that come from outside the cell and cause
changes inside of the cell as a result.
Calcium is hazardous to DNA.
Too high of a calcium concentration
will cause chromosomes to precipitate.
Well the last thing you want your
chromosomes to do inside of a cell
is to fall out of solution.
Calcium interacts as a result with proteins
that keep its concentration
from getting too high.
One of these proteins that's commonly
used is known as calmodulin.
Now, calmodulin is a protein that
is shown on the figure on the right
and it’s a very flexible protein.
You can see on the figure on the left where
the calmodulin has no calcium bound to it
and compare that with this figure
that is shown on the right
that has the calcium bound to it.
You can see a change in
shape that has happened.
And you can also see a little bit of those
EF hands that I talked about before.
In the case of the
structure on the right,
EF hand is literally holding onto
that calcium as you can see.
The shape change that occurs in
calmodulin on binding of the calcium
is the signal to other proteins inside
the cell that calcium is present.
So rather than proteins interacting
directly with calcium,
they interact with calmodulin
that has the calcium bound to it.
If they interact with the calmodulin that
doesn’t have the calcium bound to it,
the calmodulin is in the wrong shape
and the protein knows that the cell
is not signaling with calcium.
The EF hand structure, as I said,
is a very important structure.
Calmodulin has two
EF hand binding regions
and those two EF hand binding regions
each bind to one calcium ion.
Calcium can also bind to many
proteins as second messenger.
So calmodulin is only
one of the proteins
through which calcium
can exert its effects.
As I noted earlier, calcium is also the
stimulus for muscular contraction.
Causing muscles to contract
is a pretty important thing
so we don’t want muscles
and that is managed very carefully
using a specialized organelle
inside the muscle cells
known as the sarcoplasmic reticulum.
Yet one more function that
is associated with calcium
is controlling glycogen breakdown.
Now, glycogen, of course, is a very
important source of glucose in our cells.
Glucose is needed for energy.
So I want to show you very
briefly what happens with that.
In other lectures, I’ve talked
about glycogen metabolism
and I’ve talked about how
glycogen metabolism is stimulated
by action of a protein known
as phosphorylase kinase.
Calcium affects this protein.
Calcium is, as I said, the signal
for the muscles to contract
and it’s stimulating glycogen breakdown.
Now, why do I mention
and glycogen breakdown in
almost the same sentence?
Well, muscle contraction
and glucose is produced
by glycogen breakdown.
And so, when we think about the release of
calcium that happens inside of muscle cells
is not only causing a
muscle cell to contract
but it’s also stimulating the
action of phosphorylase kinase
which ultimately stimulates the breakdown
of glycogen to provide glucose,
which is energy for
the muscle cell.
Now, you can see on the figure on the
right here what’s actually happening
is the calcium is binding to calmodulin,
the upper left part of the figure.
And calmodulin is the interacting protein
that is affecting the phosphorylase kinase.
So if we look at the
figure on the far left,
we see fully inactive
Moving upwards to the upper right, we
see that we have it partially active.
And the partial activation
of that protein is happening
as a result of calcium bound to calmodulin
activating the phosphorylase kinase.
Why is it only partly active?
It’s only partly active because the
phosphorylase kinase has also be phosphorylated
and it has to have a phosphate group
attached to it to be fully active.
That happens in the process
shown at the bottom.
So the cell can either go to the
process to the bottom first,
that is phosphorylation first,
and then get the calcium added
or it can start by getting the
calcium added going up to the top
and then get phosphorylated
to get the fully active form.
What’s the difference?
Well, the difference is that the top
process occurs almost instantaneously,
as soon as calcium is released,
phosphorylase kinase is activated
and glycogen breakdown happens
If you’re taking off on a race and you want
to run fast, you need that glucose now.
You don’t need to wait for
your hormones to release,
that hormone release causes
So by having this immediate action,
kinase can give glucose
as soon as the muscle
cell actually needs it.
So, as I said, this increases
the glucose concentration.
The muscle cell is happy
and this also increases the ATP
because glucose is what’s needed
to synthesize ATP
inside the cells.
Now, calcium-calmodulin can also
act inside the muscle cells
in a sort of a cyclic
in which they also bind to
the endoplasmic reticulum
and stimulate the release
of even more calcium.
So we a sort of snowballing effect that
can happen once calcium gets released.
So with this lecture,
we have seen two very
important and interesting
vitamin A which has roles in vision and
also in the process of differentiation.
We’ve also seen vitamin D and its ability
to modulate calcium levels in the cell
as well as its ability to
control gene expression
and a variety of other functions
necessary for multicellular organisms.