>>Dr. Ketchum: In this lecture video we are going to go ahead and continue talking about
chemical messengers. And we are still focusing on membrane-bound mediated responses, and
more specifically, we’re going to focus on what a G protein-linked receptor is. So
remember, if we’re talking about membrane-mediated responses, we’re talking about lipophobic
ligands that bind to the receptors. Before we get into any mechanisms, you need to understand
the basics about a G protein-linked receptor. So you need to understand what is the structure
of a G protein. So first off, what does the G stand for, okay? This G stands for “guanosine.”
This is a nitrogenous phase. Within the intracellular fluid, so here’s the ICF of this cell, okay?
You’re looking at three subunits that make up the G protein. These include alpha, beta,
and gamma, as you can see there. Notice that you have a GDP, that’s what the guana—the
G guanasine diphosphate is attached to the alpha subunit. That’s a very important concept.
GDP is a nucleotide like ADP is a nucleotide. Okay, so to activate a G protein—how does
it get activated? So first off your messenger, your ligand, which remember has to be lipophobic,
has to bind to the receptor. So remember we’re dealing with slow responses here; so the receptor
and the channel are different proteins. So when the ligand binds to the receptor, what
happens to happen next? So in step two then, GDP falls off the alpha subunit. And when
GDP falls off the alpha subunit, GTP is added. And when GTP is added, the G protein is now
activated. And when it’s activated, it’s the alpha subunit that slides over. And when
it slides over, it will either bump into a channel or it will bump into what’s called
an amplifier enzyme. I’ll show you examples of both of these later. Now, when this G protein
is active, this can either alter enzyme activity on the cytoplasmic side of the membrane or
it can alter an ion channel. Okay? So once again we’ll come back to that later. Now
you shouldn’t leave your G protein activated, correct? Because if the G protein remains
activated, then the target cell keeps making a response, which you don’t want the target
cell to continue to do that indefinitely because then you’re no longer in homeostasis. Okay.
So to inactivate a G protein, the ligand must be removed or it must fall off the receptor.
Remember that binding to a receptor is reversible. The second thing that must happen is that
GTP must be hydrolyzed. Remember when we hydrolyzed ATP? You got an ADP and a phosphate?
The same is true here. When you hydrolyze GTP, you get a GDP plus a phosphate. So when that happens,
then your alpha subunit slides back over and all three subunits are bound once again.
So the thing is, is that you need to remember that G protein-linked receptors are an example
of a ligand gated channel. These are slow ligand gated channels, like I mentioned earlier.
And so if they’re slow, are the receptor and the channel the same protein or are they
two separate proteins? Well, they’re two separate proteins. And slow G protein-linked
receptors are involved with these two mechanisms that we will discuss. There’s
direct coupling and there’s second messenger, and we’ll be discussing each of these. So
let’s look at direct coupling first. So here in direct coupling again, you’ve got
to get your bearings. Here’s the extracellular fluid in blue, cytosol is in tan, here’s
your ligand—your messenger is your ligand. So it binds to your receptor. So then when
that happens, we know that we activate a G protein and that’s what’s going on in
step two. And we mentioned earlier how a G protein is activated. So the GDP falls off
the alpha subunit, GTP is bound to the alpha subunit, and the alpha subunit slides over
and here’s the thing: In direct coupling, that alpha subunit smacks into a channel.
Here’s our channel in pink. This channel will either open or it will close. That’s
a very important concept. When we talked about fast channels, remember, we said they only
open. In direct coupling, the channel can open or it may close. Okay, so let’s assume
that the channel opens. If the channel opens, then you can have ions move into or out of
the cell, and then that will change the electrical properties of the cell. So remember, that—that’s
one of the functions of a membrane-bound response is to change the electrical properties inside
of the cell. So that’s direct. Direct coupling—just think the alpha subunit smacks directly
into the channel. Okay, then we have the second messenger system, which is also G protein
linked. So in general, so we’re going to look at this from a broad perspective first,
second messengers are triggered by the first messenger. That’s what the ligand is, and
that activates your G protein. Nothing different so far from direct coupling, but now this
is where things differ. The G protein then is going to activate the amplifier enzyme.
And when the amplifier enzyme is activated, that’s going to activate a second messenger.
There are different types of second messengers that we’ll talk about later. The second
messenger then can either activate or inhibit cellular pathways. Okay, so here are the various
amplifier enzymes. When you say adenylyl cyclase, this is also adenylate cyclase and guanylyl
is also guanylate cyclase, and then there’s phospholipase C. And so what adenylate cyclase
does is it’s going to convert ATP to cyclic AMP. Guanylate cyclase, that amplifier enzyme
will convert GTP to cyclic GMP and phospholipase C will convert your membrane phospholipids
over to IP3 and DAG. These here on the end are your second messengers. Okay, so then
let’s take a look at the very second messenger system. So cyclic AMP, cyclic GMP are both
nucleotides. So remember what makes up a nucleotide. DAG and IP3 are lipid derived, and then there’s
calcium, which is an ion. So these are the five second messenger systems that we will
be discussing throughout the semester, and right now in a separate video I will introduce
you to the cyclic AMP second messenger system, as well as DAG, IP3, calcium. When we get
to photo transduction or when we get to the eye, vision, we will talk about the cyclic
GMP second messenger system. So that concludes this video.