So the cyclic AMP as a second messenger has
to interact with other molecules to cause
that signal to be transmitted because if
it doesn’t, then there won’t be a signal.
Well it turns out that cyclic AMP goes and
interacts with a protein known as protein kinase A.
Now protein kinase A as its name suggests is
a protein of course, and it’s also an enzyme.
But in the normal state, protein kinase A is in the
inactive form, meaning it’s not catalyzing any reaction.
And that’s because the protein kinase A has its
catalytic part of itself having been covered up.
The covering up of the catalytic part prevents
the catalytic part from catalyzing a reaction.
So we can see that in
this depiction here.
We see that protein kinase A has
four subunits associated with it.
Two units that are in red with an R in them,
indicating that they’re regulatory subunits.
And these subunits are
covering up that catalytic site.
The two C subunits in blue are where
the catalytic site is located.
Well here comes our four molecules of cyclic AMP that has been
produced by the adenylate cyclase in the previous reaction.
What happens is, these four cyclic AMPs convert the
inactive form of protein kinase A into the active form.
And the way they do that is by
binding to the regulatory subunits.
Now as we’ve seen time and again in these
lectures, binding of a molecule to a
protein, slightly changes that protein’s
shape, in this case the regulatory subunits.
And the regulatory subunits with their change in
shape can no longer bind to the catalytic subunits.
Consequently the catalytic subunits are released and now their
catalytic sites are open and exposed
to all the molecules in the cell.
They can begin to catalyse reactions.
So now we see the information from the hormone outside the
cell has been communicated all the way to protein kinase A.
And we still have a ways to go.
What protein kinase A’s catalytic subunits
do, is they catalyze the addition of
phosphates to the side chains of serine and
threonine amino acids within a protein.
This is the covalent modification
that I talked about before.
So we can see this modification happening
starting with an unphosphorylated
or unmodified protein on the left and
the modified protein on the right.
The phosphate that’s put onto the side chains of the
serines and threonines comes there from a molecule of
ATP, which transfers onto serine’s and threonine’s
side chains in a process that we call phosphorylation.
Now protein kinase A
phosphorylates many proteins.
And phosphorylating those proteins
causes their activities to change.
Protein kinase A for example, phosphorylates
proteins in glycogen metabolism.
Two of the proteins that it phosphorylates are known as
glycogen synthase, which catalyzes the formation of glycogen.
And another protein known as phosphorylase
kinase or PK, that activates glycogen breakdown.
The cell’s decision to either make
glycogen or break down glycogen comes
as a result of action of this hormone
system that I’ve described here.
Let’s watch to see what
happens in this process.
Here’s the catalytic subunit of protein kinase A that
was released in the process of the previous slide.
We can see glycogen synthase labeled in
S, and we see that it gains a phosphate.
Now in this scheme I’m showing you
here, the enzymes that are active
are shown in green, and the enzymes
that are inactive are shown in red.
So we see in this case that glycogen
synthase started out in the active form
but it got a phosphate put onto it and
that converted it into the inactive form.
But protein kinase A also works
on phosphorylase kinase as I said.
And phosphorylase kinase, when it
gains a phosphate, it’s converted
from the inactive form in red to the active form in green.
What phosphorylase kinase will do is go further
and activate the breakdown of glycogen.
So the action of this hormone signaling
system is to turn off the synthesis
of glycogen and to turn on the breakdown
of glycogen at the same time.
What active phosphorylase kinase does
is convert an enzyme known as glycogen
phosphorylase from the inactive form to the
active form by adding a phosphate to it.
So phosphorylase kinase is a protein that
can add a phosphate to another protein.
What glycogen phosphorylase a does, the
active form, is it breaks down glycogen.
And what glycogen synthase does
when it’s active is make glycogen.
So this process that I’ve described to you
here, as I said earlier is simultaneously
turning off the glycogen synthesis at the same
time as it’s turning on glycogen breakdown.
That process as I've described in a previous
lecture is known as reciprocal regulation.
The same process having opposite effects on
catalytic-- catabolic and anabolic pathways.